FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Filardy, AA Costa-da-Silva, AC Koeller, CM Guimaraes-Pinto, K Ribeiro-Gomes, FL Lopes, MF Heise, N Freire-de-Lima, CG Nunes, MP DosReis, GA AF Filardy, Alessandra A. Costa-da-Silva, Ana Caroline Koeller, Carolina M. Guimaraes-Pinto, Kamila Ribeiro-Gomes, Flavia L. Lopes, Marcela F. Heise, Norton Freire-de-Lima, Celio G. Nunes, Marise P. DosReis, George A. TI Infection with Leishmania major Induces a Cellular Stress Response in Macrophages SO PLOS ONE LA English DT Article ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; FAS LIGAND; TNF-ALPHA; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; T-LYMPHOCYTES; MAP KINASES; EXPRESSION; MICE AB We investigated early cellular responses induced by infection with Leishmania major in macrophages from resistant C57/BL6 mice. Infection increased production of reactive oxygen species by resident, but not inflammatory peritoneal macrophages. In addition, infection increased activation of stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) in resident, but not in inflammatory peritoneal macrophages. Infection also increased expression of membrane and soluble FasL, but infected macrophages remained viable after 48 h. Infection increased secretion of cytokines/chemokines TNF-alpha, IL-6, TIMP-1, IL-1RA, G-CSF, TREM, KC, MIP-1 alpha, MIP-1 beta, MCP-1, and MIP-2 in resident macrophages. Addition of antioxidants deferoxamine and N-acetylcysteine reduced ROS generation and JNK activation. Addition of antioxidants or JNK inhibitor SP600125 reduced secretion of KC. Furthermore, treatment with antioxidants or JNK inhibitor also reduced intracellular parasite replication. These results indicated that infection triggers a rapid cellular stress response in resident macrophages which induces proinflammatory signals, but is also involved in parasite survival and replication in host macrophages. C1 [Filardy, Alessandra A.; Costa-da-Silva, Ana Caroline; Koeller, Carolina M.; Guimaraes-Pinto, Kamila; Lopes, Marcela F.; Heise, Norton; Freire-de-Lima, Celio G.; DosReis, George A.] Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Rio De Janeiro, Brazil. [Ribeiro-Gomes, Flavia L.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Nunes, Marise P.] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro, Brazil. RP DosReis, GA (reprint author), Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Rio De Janeiro, Brazil. EM gdosreis@biof.ufrj.br RI lopes, marcela/E-2201-2012; Ribeiro-Gomes, Flavia/F-7609-2015 OI lopes, marcela/0000-0002-4508-0505; FU Brazilian National Research Council (CNPq); Rio de Janeiro State Science Foundation (FAPERJ); Programa Institutos Nacionais de Ciencia e Tecnologia (INCT), CNPq, Brazil FX This work was supported by Brazilian National Research Council (CNPq), Rio de Janeiro State Science Foundation (FAPERJ), and Programa Institutos Nacionais de Ciencia e Tecnologia (INCT), CNPq, Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 9 Z9 9 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2014 VL 9 IS 1 AR e85715 DI 10.1371/journal.pone.0085715 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291XP UT WOS:000329866300100 PM 24416445 ER PT J AU Roth, TL Nayak, D Atanasijevic, T Koretsky, AP Latour, LL McGavern, DB AF Roth, Theodore L. Nayak, Debasis Atanasijevic, Tatjana Koretsky, Alan P. Latour, Lawrence L. McGavern, Dorian B. TI Transcranial amelioration of inflammation and cell death after brain injury SO NATURE LA English DT Article ID GREEN FLUORESCENT PROTEIN; IN-VIVO; STERILE INFLAMMATION; HEAD-INJURY; MICE; BIOMARKERS; INSERTION; RELEASE; CORTEX; FLUID AB Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function(1,2). At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury. C1 [Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP McGavern, DB (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov RI Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; McGavern, Dorian/0000-0001-9568-545X; Roth, Theodore/0000-0002-3970-9573 FU National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS); Center for Neuroscience and Regenerative Medicine (CNRM) at the Uniformed Services University of the Health Sciences; NIH; Department of Defense; Walter Reed National Military Medical Center FX The study was supported by the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS), and the Center for Neuroscience and Regenerative Medicine (CNRM) at the Uniformed Services University of the Health Sciences-a collaborative effort between the NIH, the Department of Defense and the Walter Reed National Military Medical Center to develop innovative approaches for brain injury diagnosis and recovery. NR 26 TC 100 Z9 101 U1 8 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 9 PY 2014 VL 505 IS 7482 BP 223 EP + DI 10.1038/nature12808 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286CG UT WOS:000329441500040 PM 24317693 ER PT J AU Porucznik, CA Cox, KJ Schliep, KC Stanford, JB AF Porucznik, Christina A. Cox, Kyley J. Schliep, Karen C. Stanford, Joseph B. TI Pilot test and validation of the Peak Day method of prospective determination of ovulation against a handheld urine hormone monitor SO BMC WOMENS HEALTH LA English DT Article DE Environmental exposure; Epidemiology; Ovulation; Fertilization; Validation studies; Luteinizing hormone; Biomonitoring ID PERICONCEPTIONAL MULTIVITAMIN USE; PROSPECTIVE MULTICENTER TRIAL; MENSTRUAL-CYCLE; FERTILE WINDOW; PROSPECTIVE PREGNANCY; ORAL-CONTRACEPTIVES; MUCUS OBSERVATIONS; CERVICAL-MUCUS; EXPOSURE; RISK AB Background: Transient exposures may influence fertility and early embryonic development. To assess the time of conception in vivo and conduct concurrent biomonitoring, ovulation must be identified prospectively. We report on the development and validation of a simple, prospective method, the Peak Day method, to determine likely day of ovulation based upon daily observations of cervical fluid. Methods: We recruited 98 women to learn the Peak Day method from a brochure, 26 of whom concurrently used the method with blinded daily urine hormone monitoring (estrone glucuronide and luteinizing hormone). All women were instructed to complete an exposure questionnaire immediately upon identifying ovulation. Briefly, the exposure questionnaire captured time-varying and transient exposures such as medication use, water consumption, and amount of sleep. We assessed timely completion of the exposure questionnaire, agreement of women's estimated day of ovulation (EDO) and the EDO by expert review, and agreement between the EDO by expert review and by blinded urine monitoring. Results: Of 147 cycles evaluated, women selected an EDO in 130 (88%) and subsequently completed the periovulatory exposure questionnaire in 122 (94%) cycles. Of the 26 cycles evaluated with blinded hormonal monitoring, the Peak Day "best quality" algorithm, based upon cervical fluid, identified ovulation +/- 3 days of the urine monitor in 24 cycles (92%). Conclusions: With simple written instructions, women can identify an estimated day of ovulation and perform periovulatory exposure assessment. The Peak Day method is highly cost-effective and could be applied by researchers to target periconceptional or very early developmental stage exposure assessment. C1 [Porucznik, Christina A.; Cox, Kyley J.; Stanford, Joseph B.] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. [Schliep, Karen C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Porucznik, CA (reprint author), Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. EM christy.porucznik@utah.edu FU Primary Children's Foundation (Salt Lake City, UT); University of Utah Department of Family and Preventive Medicine Health Studies Fund FX This work was supported by a grant from the Primary Children's Foundation (Salt Lake City, UT), and the University of Utah Department of Family and Preventive Medicine Health Studies Fund. Partial support for all datasets within the Utah Population Database is being provided by the Huntsman Cancer Institute. We would like to thank Swiss Precision Diagnostics GmbH (http://www.swissprecisiondiagnostics.com/brands.php) for creating and making available the blinded urine hormone monitors used for the validation study. Experts who consulted with us on development of the Peak Day method were: Thomas Hilgers, Creighton University; Victoria Jennings, Georgetown University; and Toni Weschler. NR 54 TC 3 Z9 3 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6874 J9 BMC WOMENS HEALTH JI BMC Womens Health PD JAN 8 PY 2014 VL 14 AR 4 DI 10.1186/1472-6874-14-4 PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology GA AB7NC UT WOS:000331976200001 PM 24400707 ER PT J AU Huang, B Huang, SG Su, XZ Guo, H Xu, YC Xu, F Hu, XC Yang, YM Wang, SQ Lu, FL AF Huang, Bo Huang, Shiguang Su, Xin-zhuan Guo, Hong Xu, Yucheng Xu, Fei Hu, Xuchu Yang, Yaming Wang, Shanqing Lu, Fangli TI Genetic diversity of Plasmodium vivax population in Anhui province of China SO MALARIA JOURNAL LA English DT Article DE Plasmodium vivax; pvmsp-1; pvmsp-3a; pvcsp; Anhui; China ID MEROZOITE SURFACE PROTEIN-3-ALPHA; HUMAN MALARIA PARASITE; CIRCUMSPOROZOITE PROTEIN; ALLELIC RECOMBINATION; ANOPHELES-SINENSIS; VARIANTS VK210; POLYMORPHISM; AREAS; VK247; INFECTIONS AB Background: Although the numbers of malaria cases in China have been declining in recent years, outbreaks of Plasmodium vivax malaria were still being reported in rural areas south of the Yellow River. To better understand the transmission dynamics of P. vivax parasites in China, the extent of genetic diversity of P. vivax populations circulating in Bozhou of Anhui province of China were investigated using three polymorphic genetic markers: merozoite surface proteins 1 and 3 alpha (pvmsp-1 and pvmsp-3 alpha) and circumsporozoite protein (pvcsp). Methods: Forty-five P. vivax clinical isolates from Bouzhou of Anhui province were collected from 2009 to 2010 and were analysed using PCR/RFLP or DNA sequencing. Results: Seven and six distinct allelic variants were identified using PCR/RFLP analysis of pvmsp-3 alpha with HhaI and AluI, respectively. DNA sequence analysis of pvmsp-1 (variable block 5) revealed that there were Sal-I and recombinant types but not Belem type, and seven distinct allelic variants in pvmsp-1 were detected, with recombinant subtype 2 (R2) being predominant (66.7%). All the isolates carried pvcsp with VK210 type but not VK247 or P. vivax-like types in the samples. Sequence analysis of pvcsp gene revealed 12 distinct allelic variants, with VK210-1 being predominant (41.5%). Conclusions: The present data indicate that there is some degree of genetic diversity among P. vivax populations in Anhui province of China. The genetic data obtained may assist in the surveillance of P. vivax infection in endemic areas or in tracking potential future disease outbreak. C1 [Huang, Bo; Hu, Xuchu; Lu, Fangli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China. [Huang, Bo; Hu, Xuchu; Lu, Fangli] Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China. [Huang, Shiguang] Jinan Univ, Sch Med, Guangzhou 510632, Guangdong, Peoples R China. [Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China. [Guo, Hong] Hainan Med Univ, Publ Lab, Haikou 571199, Hainan, Peoples R China. [Xu, Yucheng; Xu, Fei] Licang Town Hosp Mengcheng Cty, Clin Lab, Licang 233500, Anhui, Peoples R China. [Yang, Yaming] Yunnan Inst Parasit Dis, Puer 665000, Yunnan, Peoples R China. [Wang, Shanqing] Hainan CDC, Haikou 570203, Hainan, Peoples R China. RP Lu, FL (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China. EM fanglilu@yahoo.com OI Su, Xinzhuan/0000-0003-3246-3248 FU Fogarty International Center of the National Institutes of Health [R01TW008151]; Divisions of Intramural Research at the National Institute of Allergy and Infectious Diseases, National Institutes of Health; State Bureau of Foreign Experts and Ministry of Education of China [B12003]; "111 Project" FX Research reported in this publication was supported in part by the Fogarty International Center of the National Institutes of Health under Award Number R01TW008151, the Divisions of Intramural Research at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the "111 Project" sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (no. B12003). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Cindy Clark at NIH Library Writing Center for editing. NR 49 TC 8 Z9 8 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD JAN 8 PY 2014 VL 13 AR 13 DI 10.1186/1475-2875-13-13 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 297IJ UT WOS:000330248800003 PM 24401153 ER PT J AU Ciccocioppo, R de Guglielmo, G Hansson, AC Ubaldi, M Kallupi, M Cruz, MT Oleata, CS Heilig, M Roberto, M AF Ciccocioppo, Roberto de Guglielmo, Giordano Hansson, Anita C. Ubaldi, Massimo Kallupi, Marsida Cruz, Maureen T. Oleata, Christopher S. Heilig, Markus Roberto, Marisa TI Restraint Stress Alters Nociceptin/Orphanin FQ and CRF Systems in the Rat Central Amygdala: Significance for Anxiety-Like Behaviors SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; AMINOBUTYRIC-ACID RELEASE; CENTRAL EXTENDED AMYGDALA; BED NUCLEUS; GABAERGIC TRANSMISSION; STRIA TERMINALIS; SEEKING BEHAVIOR; INDUCED ANOREXIA; ETHANOL; RECEPTOR AB Corticotropin releasing factor (CRF) is the primary mediator of stress responses, and nociceptin/orphanin FQ (N/OFQ) plays an important role in the modulation of these stress responses. Thus, in this multidisciplinary study, we explored the relationship between the N/OFQ and the CRF systems in response to stress. Using in situ hybridization (ISH), we assessed the effect of body restraint stress on the gene expression of CRF and N/OFQ-related genes in various subdivisions of the amygdala, a critical brain structure involved in the modulation of stress response and anxiety-like behaviors. We found a selective upregulation of the NOP and downregulation of the CRF1 receptor transcripts in the CeA and in the BLA after body restraint. Thus, we performed intracellular electrophysiological recordings of GABAA-mediated IPSPs in the central nucleus of the amygdala (CeA) to explore functional interactions between CRF and N/OFQ systems in this brain region. Acute application of CRF significantly increased IPSPs in the CeA, and this enhancement was blocked by N/OFQ. Importantly, in stress-restraint rats, baseline CeA GABAergic responses were elevated and N/OFQ exerted a larger inhibition of IPSPs compared with unrestraint rats. The NOP antagonist [Nphe1]-nociceptin(1-13) NH2 increased the IPSP amplitudes in restraint rats but not in unrestraint rats, suggesting a functional recruitment of the N/OFQ system after acute stress. Finally, we evaluated the anxiety-like response in rats subjected to restraint stress and nonrestraint rats after N/OFQ microinjection into the CeA. Intra-CeA injections of N/OFQ significantly and selectively reduced anxiety-like behavior in restraint rats in the elevated plus maze. These combined results demonstrate that acute stress increases N/OFQ systems in the CeA and that N/OFQ has antistress properties. C1 [Ciccocioppo, Roberto; de Guglielmo, Giordano; Ubaldi, Massimo; Kallupi, Marsida] Univ Camerino, Pharmacol Unit, Sch Pharm, I-62032 Camerino, Italy. [Hansson, Anita C.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, D-68159 Heidelberg, Germany. [Kallupi, Marsida; Cruz, Maureen T.; Oleata, Christopher S.; Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Heilig, Markus] NIAAA, NIH, Bethesda, MD 20892 USA. RP Roberto, M (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. EM roberto.cicccocioppo@unicam.it; mroberto@scripps.edu OI Ubaldi, Massimo/0000-0002-4089-2483; Kallupi, Marsida/0000-0002-8688-709X FU National Institutes of Health [AA017447, AA015566, AA06420, AA016985, AA014351, AA013498, AA021491]; Pearson Center for Alcoholism and Addiction Research; Deutsche Forschungsgemeinschaft [HA 6102/1] FX This work was supported by National Institutes of Health Grants AA017447, AA015566, AA06420, AA016985, AA014351, AA013498, and AA021491 and the Pearson Center for Alcoholism and Addiction Research. A. C. H. was supported by Deutsche Forschungsgemeinschaft HA 6102/1. We thank Dr Marian Logrip for helpful comments on the manuscript. NR 37 TC 16 Z9 16 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 8 PY 2014 VL 34 IS 2 BP 363 EP 372 DI 10.1523/JNEUROSCI.2400-13.2014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 290XH UT WOS:000329791300005 PM 24403138 ER PT J AU Skibinski, G Nakamura, K Cookson, MR Finkbeiner, S AF Skibinski, Gaia Nakamura, Ken Cookson, Mark R. Finkbeiner, Steven TI Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies SO JOURNAL OF NEUROSCIENCE LA English DT Article DE LRRK2; mechanisms; Parkinson's disease; single cell; synuclein ID DISEASE-ASSOCIATED MUTATIONS; CHAPERONE-MEDIATED AUTOPHAGY; LACKING ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; DOPAMINE NEURONS; KNOCKOUT MICE; NEURODEGENERATIVE DISEASE; CYTOPLASMIC LOCALIZATION; SURVIVAL ANALYSIS; COMPETING RISK AB By combining experimental neuron models and mathematical tools, we developed a "systems" approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. C1 [Skibinski, Gaia; Nakamura, Ken; Finkbeiner, Steven] Taube Koret Ctr Neurodegenerat Dis Res, Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA. [Skibinski, Gaia; Nakamura, Ken; Finkbeiner, Steven] Hellman Family Fdn Program Alzheimers Dis Res, San Francisco, CA 94158 USA. [Nakamura, Ken; Finkbeiner, Steven] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA. [Nakamura, Ken; Finkbeiner, Steven] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA. [Nakamura, Ken; Finkbeiner, Steven] Univ Calif San Francisco, Grad Program Biomed Sci, San Francisco, CA 94158 USA. [Cookson, Mark R.] NIH, Neurogenet Lab, Bethesda, MD 20892 USA. RP Finkbeiner, S (reprint author), Gladstone Inst Neurol Dis, 1650 Owens St,Room 308, San Francisco, CA 94158 USA. EM sfinkbeiner@gladstone.ucsf.edu FU National Center for Research Resources Grant [RR18928]; Hillblom Foundation; Burroughs-Wellcome Medical Scientist Fund Career Award, NINDS [1K08NS062954-01A1]; National Institute of Neurological Disorders and Stroke [P30NS069496]; Intramural Research Program of the NIH, National Institute on Aging; Koret/Taube Center; Hellman Family Foundation; [U24 NS078370]; [3R01 NS039074]; [2R01 NS04549]; [2P01 AG0224074]; [CIRM RB4-06079] FX This work was supported with a gift from the DeClerq family in memory of Betty Brown. The Gladstone Institutes received support from a National Center for Research Resources Grant RR18928. G.S. is supported by the Hillblom Foundation. K.N. is supported by the Burroughs-Wellcome Medical Scientist Fund Career Award, NINDS (1K08NS062954-01A1) and award no. P30NS069496 from the National Institute of Neurological Disorders and Stroke. M.R.C. is supported in part by the Intramural Research Program of the NIH, National Institute on Aging. S.F. is supported by Grants U24 NS078370, 3R01 NS039074, 2R01 NS04549, 2P01 AG0224074, CIRM RB4-06079 research Grant, the Koret/Taube Center, and the Hellman Family Foundation. We thank members of the Finkbeiner lab for useful discussions, A. L. Lucido, S. Ordway, and G. Howard for editorial assistance, and K. Nelson for administrative assistance. Dr. Dario Alessi (MRC-PPU, Dundee University, Dundee Scotland) who kindly provided LRRK2-IN1 and rabbit monoclonal anti-LRRK2 (100-500), anti-LRRK2 P-ser935, or anti-LRRK2 P-ser910. NR 83 TC 33 Z9 33 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 8 PY 2014 VL 34 IS 2 BP 418 EP 433 DI 10.1523/JNEUROSCI.2712-13.2014 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 290XH UT WOS:000329791300009 PM 24403142 ER PT J AU Wyeth, MS Pelkey, KA Petralia, RS Salter, MW McInnes, RR McBain, CJ AF Wyeth, Megan S. Pelkey, Kenneth A. Petralia, Ronald S. Salter, Michael W. McInnes, Roderick R. McBain, Chris J. TI Neto Auxiliary Protein Interactions Regulate Kainate and NMDA Receptor Subunit Localization at Mossy Fiber-CA3 Pyramidal Cell Synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE electron microscopy; kainate receptor; metabotropic; mossy fiber pathway; Neto1 or Neto2; NMDAR ID GLUTAMATE RECEPTORS; MODULATION AB Neto1 and Neto2 auxiliary subunits coassemble with NMDA receptors (NMDARs) and kainate receptors (KARs) to modulate their function. In the hippocampus, Neto1 enhances the amplitude and prolongs the kinetics of KAR-mediated currents at mossy fiber (MF)-CA3 pyramidal cell synapses. However, whether Neto1 trafficks KARs to synapses or simply alters channel properties is unresolved. Therefore, postembedding electron microscopy was performed to investigate the localization of GluK2/3 subunits at MF-CA3 synapses in Neto-null mice. Postsynaptic GluK2/3 Immunogold labeling was substantially reduced in Neto-null mice compared with wild types. Moreover, spontaneous KAR-mediated synaptic currents and metabotropic KAR signaling were absent in CA3 pyramidal cells of Neto-null mice. A similar loss of ionotropic and metabotropic KAR function was observed in Neto1, but not Neto2, single knock-out mice, specifically implicating Neto1 in regulating CA3 pyramidal cell KAR localization and function. Additional controversy pertains to the role of Neto proteins in modulating synaptic NMDARs. While Immunogold labeling for GluN2A at MF-CA3 synapses was comparable between wild-type and Neto-null mice, labeling for postsynaptic GluN2B was robustly increased in Neto-null mice. Accordingly, NMDAR-mediated currents at MF-CA3 synapses exhibited increased sensitivity to a GluN2B-selective antagonist in Neto1 knockouts relative to wild types. Thus, despite preservation of the overall MF-CA3 synaptic NMDAR-mediated current, loss of Neto1 alters NMDAR subunit composition. These results confirm that Neto protein interactions regulate synaptic localization of KAR and NMDAR subunits at MF-CA3 synapses, with implications for both ionotropic and metabotropic glutamatergic recruitment of the CA3 network. C1 [Wyeth, Megan S.; Pelkey, Kenneth A.; McBain, Chris J.] NICHHD, Eunice Kennedy Shriver Natl Inst, NIH, Bethesda, MD 20892 USA. [Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Salter, Michael W.] Univ Toronto, Program Neurosci & Mental Hlth, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Salter, Michael W.] Univ Toronto, Dept Physiol, Toronto, ON M5G 1X8, Canada. [McInnes, Roderick R.] McGill Univ, Lady Davis Res Inst, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [McInnes, Roderick R.] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. [McInnes, Roderick R.] McGill Univ, Dept Biochem, Montreal, PQ H3T 1E2, Canada. RP McBain, CJ (reprint author), NICHD, Program Dev Neurobiol, Sect Cellular & Synapt Neurophysiol, NIH, Porter Neurosci Bldg,Room 3C903,35 Lincoln Dr,MSC, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov FU National Institute of Child Health and Human Development Intramural Research Program; National Institute on Deafness and Other Communication Disorders Intramural Research Program; NIGMS Intramural Postdoctoral Research Associate Fellowship; Canada Research Chair; Anne and Max Tanenbaum Chair in Molecular Medicine; Canadian Institutes of Health Research [MOP-7315, IOP-54037] FX C.J.M. was supported by the National Institute of Child Health and Human Development Intramural Research Program; R. S. P. was supported by the National Institute on Deafness and Other Communication Disorders Intramural Research Program; M.S.W. was supported by an NIGMS Intramural Postdoctoral Research Associate Fellowship; M.W.S. was supported by a Canada Research Chair, and the Anne and Max Tanenbaum Chair in Molecular Medicine; and R.R.M. was supported by Canadian Institutes of Health Research Grants MOP-7315 and IOP-54037, and a Canada Research Chair. We thank Ya-Xian Wang for help with electron microscopy. NR 23 TC 17 Z9 17 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 8 PY 2014 VL 34 IS 2 BP 622 EP 628 DI 10.1523/JNEUROSCI.3098-13.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 290XH UT WOS:000329791300027 PM 24403160 ER PT J AU Censor, N Horovitz, SG Cohen, LG AF Censor, Nitzan Horovitz, Silvina G. Cohen, Leonardo G. TI Interference with Existing Memories Alters Off line Intrinsic Functional Brain Connectivity SO NEURON LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY MOTOR CORTEX; BASAL GANGLIA; DECLARATIVE MEMORY; TIME-COURSE; RECONSOLIDATION; CONSOLIDATION; SKILL; MECHANISMS; HUMANS AB The notion that already existing memories can be modified after their reactivation has received an increasing amount of experimental support, with empirical data accumulating across species and memory paradigms. However, there is no evidence for systems-level task-free intrinsic signatures of memory modification. Here, using a combination of behavioral, brain stimulation, and neuroimaging paradigms, we report that noninvasive transcranial magnetic stimulation interference with a reactivated motor memory altered offline task-free corticostriatal interregional functional connectivity, reducing it compared to stimulation in which the reactivated memory was intact. Furthermore, the modulated functional connectivity predicted offline memory modification. This reduction in functional connectivity recovered after additional execution of the memorized task, and the interference did not affect control cerebellar-cortical functional connectivity. This demonstrates that intrinsic task-free offline brain activity can be modulated by noninvasive interaction with existing memories and strongly correlates with behavioral measurements of changes in memory strength. C1 [Censor, Nitzan; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Horovitz, Silvina G.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Censor, N (reprint author), NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. EM censorn@ninds.nih.gov; cohenl@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS), NIH; NINDS Ruth L. Kirschstein National Research Service Award (NRSA) FX We thank Eran Dayan for his advice. This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS), NIH. N.C. was supported by an NINDS Ruth L. Kirschstein National Research Service Award (NRSA). NR 46 TC 17 Z9 17 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JAN 8 PY 2014 VL 81 IS 1 BP 69 EP 76 DI 10.1016/j.neuron.2013.10.042 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 287RD UT WOS:000329559000009 PM 24411732 ER PT J AU Prasad, V Ioannidis, JPA AF Prasad, Vinay Ioannidis, John P. A. TI Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices SO IMPLEMENTATION SCIENCE LA English DT Editorial Material DE Evidence-based medicine; Reversals; Divestment; De-implementation; Contradiction; Bias ID PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED-CONTROLLED-TRIALS; CLINICAL-PRACTICE GUIDELINES; MEDICAL THERAPY; RESISTANT-BACTERIA; ARTERY-DISEASE; ICU; INFECTIONS; INNOVATION; APPROVAL AB Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases. C1 [Prasad, Vinay] NCI, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA. EM jioannid@stanford.edu NR 31 TC 39 Z9 39 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JAN 8 PY 2014 VL 9 AR 1 DI 10.1186/1748-5908-9-1 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 290XV UT WOS:000329792800001 PM 24398253 ER PT J AU Jin, TC Wang, Y Chen, YW Fu, TJ Kothary, MH McHugh, TH Zhang, YZ AF Jin, Tengchuan Wang, Yang Chen, Yu-Wei Fu, Tong-Jen Kothary, Mahendra H. McHugh, Tara H. Zhang, Yuzhu TI Crystal Structure of Korean Pine (Pinus koraiensis) 7S Seed Storage Protein with Copper Ligands SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 7S vicilin; pine nut; allergen; X-ray crystallography; copper protein ID MAJOR PEANUT ALLERGEN; ARA H 1; TREE NUT ALLERGENS; CHEMICAL-COMPOSITION; MOLECULAR GRAPHICS; FOOD ALLERGY; PROGRAM; VICILIN; CRYSTALLIZATION; PURIFICATION AB The prevalence of food allergy has increased in recent years, and Korean pine vicilin is a potential food allergen. We have previously reported the crystallization of Korean pine vicilin purified from raw pine nut. Here we report the isolation of vicilin mRNA and the crystal structure of Korean pine vicilin at 2.40 angstrom resolution. The overall structure of pine nut vicilin is similar to the structures of other 7S seed storage proteins and consists of an N-terminal domain and a C-terminal domain. Each assumes a cupin fold, and they are symmetrically related about a pseudodyad axis. Three vicilin molecules form a doughnut-shaped trimer through head-to-tail association. Structure characterization of Korean pine nut vicilin unexpectedly showed that, in its native trimeric state, the vicilin has three copper ligands. Sequence alignments suggested that the copper-coordinating residues were conserved in winter squash, sesame, tomato, and several tree nuts, while they were not conserved in a number of legumes, including peanut and soybean. Additional studies are needed to assess whether the copper-coordinating property of vicilins has a biological function in the relevant plants. The nutritional value of this copper-coordinating protein in tree nuts and other edible seeds may be worth further investigations. C1 [Jin, Tengchuan; Wang, Yang; Chen, Yu-Wei] IIT, Dept Biol, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [McHugh, Tara H.; Zhang, Yuzhu] ARS, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. RP Jin, TC (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tengchuan@gmail.com; yuzhu.zhang@ars.usda.gov RI Jin, Tengchuan/B-5883-2014; OI Jin, Tengchuan/0000-0002-1395-188X; Zhang, Yuzhu/0000-0001-7882-5692 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Illinois Institute of Technology; U.S. Food and Drug Administration [5U01FD003801]; Institute for Food Safety and Health, Illinois Institute of Technology [5U01FD003801] FX Use of the APS was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. This work was partially supported by a fund from the Illinois Institute of Technology and by Cooperative Agreement 5U01FD003801 between the U.S. Food and Drug Administration and Institute for Food Safety and Health, Illinois Institute of Technology. NR 55 TC 7 Z9 7 U1 3 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JAN 8 PY 2014 VL 62 IS 1 BP 222 EP 228 DI 10.1021/jf4039887 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 288BK UT WOS:000329586800028 PM 24328105 ER PT J AU Promsote, W Veeranan-Karmegam, R Ananth, S Shen, D Chan, CC Lambert, NA Ganapathy, V Martin, PM AF Promsote, Wanwisa Veeranan-Karmegam, Rajalakshmi Ananth, Sudha Shen, Defen Chan, Chi-Chao Lambert, Nevin A. Ganapathy, Vadivel Martin, Pamela M. TI L-2-oxothiazolidine-4-carboxylic acid attenuates oxidative stress and inflammation in retinal pigment epithelium SO MOLECULAR VISION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; MACULAR DEGENERATION; CYSTEINE PRODRUG; NICOTINIC-ACID; AQUEOUS-HUMOR; CELLS; EXPRESSION; GLUTATHIONE; RECEPTOR AB Purpose: Oxidant-and inflammation-induced damage to retinal pigment epithelial (RPE) cells is central to the pathogenesis of age-related macular degeneration (AMD). Thus, developing novel strategies to protect these cells is important. We reported previously on the robust antioxidant and therefore cell-protective effects of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (OTC) in cultured human RPE cells. New reports citing a novel anti-inflammatory role for OTC in addition to the known glutathione-stimulating and antioxidant properties emerged recently; however, this role has not been evaluated in RPE cells or in intact retina. Given the crucial causative roles of oxidative stress and inflammation in AMD pathogenesis, knowing whether OTC might exhibit a similar benefit in this cell and tissue type has high clinical relevance; thus, we evaluated OTC in the present study. Methods: ARPE-19 and primary RPE cells isolated from wild-type, Gpr109a(-/-), or Slc5a8(-/-) mouse eyes were exposed to TNF-alpha in the presence or absence of OTC, followed by analysis of IL-6 and Ccl2 expression with real-time quantitative polymerase chain reaction or enzyme-linked immunosorbent assay. Cellular and molecular markers of inflammation and oxidative stress (i.e., IL-1 beta, TGF-beta, ABCG1, ABCA1, reduced glutathione, and dihydroethidium) were evaluated in Ccl2(-/-)/Cx3cr1(-/-) double knockout mice on rd8 background (DKO rd8) treated with OTC (10 mg/ml) in drinking water for a period of 5 months. Results: OTC treatment significantly inhibited the expression and secretion of IL-6 and Ccl2 in TNF-alpha-stimulated ARPE-19 cells. Studies conducted using DKO rd8 animals treated with OTC in drinking water confirmed these findings. Cellular and molecular markers of inflammation were significantly suppressed in the retinas of the OTC-treated DKO rd8 animals. Subsequent in vitro and in vivo studies of the possible mechanism(s) to explain these actions revealed that although OTC is an agonist of the anti-inflammatory G-protein coupled receptor GPR109A and a transportable substrate of the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8), these properties may play a role but do not explain entirely the anti-inflammatory effects this compound elicits in cultured RPE cells and the intact mouse retina. Conclusions: This study represents, to our knowledge, the first report of the suppressive effects of OTC on inflammation in cultured RPE cells and on inflammation and oxidative stress in the retina in vivo. C1 [Promsote, Wanwisa; Veeranan-Karmegam, Rajalakshmi; Ananth, Sudha; Ganapathy, Vadivel; Martin, Pamela M.] Georgia Regents Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. [Shen, Defen; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lambert, Nevin A.] Georgia Regents Univ, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA. [Martin, Pamela M.] Dept Ophthalmol, Augusta, GA 30912 USA. [Martin, Pamela M.] Georgia Regents Univ, Augusta, GA 30912 USA. [Ganapathy, Vadivel; Martin, Pamela M.] Georgia Regents Univ, James & Jean Culver Vis Discovery Inst, Augusta, GA 30912 USA. RP Martin, PM (reprint author), Georgia Regents Univ, 1410 Laney Walker Blvd,CN-1160, Augusta, GA 30912 USA. EM pmmartin@gru.edu FU James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA FX This work was supported by a Pilot Project Award from the James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA. NR 61 TC 6 Z9 6 U1 0 U2 4 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JAN 7 PY 2014 VL 20 BP 73 EP 88 PG 16 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA AB5JQ UT WOS:000331825100001 PM 24426777 ER PT J AU Yang, CZ Swallows, CL Zhang, C Lu, J Xiao, HB Brady, RO Zhuang, ZP AF Yang, Chunzhang Swallows, Cody L. Zhang, Chao Lu, Jie Xiao, Hongbin Brady, Roscoe O. Zhuang, Zhengping TI Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating molecular chaperones SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; HEAT-SHOCK RESPONSE; HSP90 INHIBITOR; THERAPEUTIC TARGET; ENZYME REPLACEMENT; CELL-SURVIVAL; BAG3 PROTEIN; CANCER; DEGRADATION; TRITERPENE AB Gaucher disease is caused bymutations in the glucosidase, beta, acid gene that encodes glucocerebrosidase (GCase). Glucosidase, beta, acid mutations often cause protein misfolding and quantitative loss of GCase. In the present study, we found that celastrol, an herb derivative with known anticancer, anti-inflammatory, and antioxidant activity, significantly increased the quantity and catalytic activity of GCase. Celastrol interfered with the establishment of the heat-shock protein 90/Hsp90 cochaperone Cdc37/Hsp90-Hsp70-organizing protein chaperone complex with mutant GCase and reduced heat-shock protein 90-associated protein degradation. In addition, celastrol modulated the expression of molecular chaperones. Bcl2-associated athanogene 3 and heat shock 70kDa proteins 1A and 1B were significantly increased by celastrol. Furthermore, BAG family molecular chaperone regulator 3 assisted protein folding and maturation of mutant GCase. These findings provide insight into a therapeutic strategy for Gaucher disease and other human disorders that are associated with protein misfolding. C1 [Yang, Chunzhang; Swallows, Cody L.; Zhang, Chao; Lu, Jie; Brady, Roscoe O.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Xiao, Hongbin] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. RP Yang, CZ (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM yangc2@ninds.nih.gov; bradyr@ninds.nih.gov; zhuangp@ninds.nih.gov FU Intramural Research Program at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH); NIH Medical Research Scholars Program; NIH; Pfizer, Inc.; Doris Duke Charitable Foundation; Alexandria Real Estate Equities, Inc.; Howard Hughes Medical Research Institute FX This work was supported by the Intramural Research Program at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) and the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer, Inc., the Doris Duke Charitable Foundation, Alexandria Real Estate Equities, Inc., and Mr. and Mrs. Joel S. Marcus and the Howard Hughes Medical Research Institute, as well as other private donors. For a complete list, please visit http://fnih.org/work/education-training-0/medical-research-scholars-prog ram. NR 54 TC 15 Z9 15 U1 3 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 2014 VL 111 IS 1 BP 249 EP 254 DI 10.1073/pnas.1321341111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700071 PM 24351928 ER PT J AU Falcon, J Coon, SL Besseau, L Cazamea-Catalan, D Fuentes, M Magnanou, E Paulin, CH Boeuf, G Sauzet, S Jorgensen, EH Mazan, S Wolf, YI Koonin, EV Steinbach, PJ Hyodo, S Klein, DC AF Falcon, Jack Coon, Steven L. Besseau, Laurence Cazamea-Catalan, Damien Fuentes, Michael Magnanou, Elodie Paulin, Charles-Hubert Boeuf, Gilles Sauzet, Sandrine Jorgensen, Even H. Mazan, Sylvie Wolf, Yuri I. Koonin, Eugene V. Steinbach, Peter J. Hyodo, Susumu Klein, David C. TI Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARYLALKYLAMINE-N-ACETYLTRANSFERASE; PINEAL-GLAND; DOCOSAHEXAENOIC ACID; ANGSTROM RESOLUTION; PETROMYZON-MARINUS; EC 2.3.1.87; MELATONIN; SEROTONIN; COMPLEX; ENZYME AB Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night: circulating levels at night are markedly higher than day levels. This increase is driven by precisely regulated increases in acetylation of serotonin in the pineal gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the synthesis of melatonin. This unique essential role of AANAT in vertebrate timekeeping is recognized by the moniker the timezyme. AANAT is also found in the retina, where melatonin is thought to play a paracrine role. Here, we focused on the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and Chondrichthyes (catshark and elephant shark) were cloned, and it was found that pineal glands and retinas from these groups express a form of AANAT that is compositionally, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT). Examination of the available genomes indicates that VT-AANAT is absent from other forms of life, including the Cephalochordate amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over one-half billion years ago. The emergence of VT-AANAT apparently involved a dramatic acceleration of evolution that accompanied neofunctionalization after a duplication of the nonvertebrate AANAT gene. This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment. C1 [Falcon, Jack; Besseau, Laurence; Cazamea-Catalan, Damien; Fuentes, Michael; Magnanou, Elodie; Paulin, Charles-Hubert; Boeuf, Gilles; Sauzet, Sandrine] CNRS, Unite Mixte Rech 7232, F-66650 Banyuls Sur Mer, France. [Falcon, Jack; Besseau, Laurence; Cazamea-Catalan, Damien; Fuentes, Michael; Magnanou, Elodie; Paulin, Charles-Hubert; Boeuf, Gilles; Sauzet, Sandrine] Univ Paris 06, Lab Arago, F-66650 Banyuls Sur Mer, France. [Coon, Steven L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Steinbach, Peter J.] NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. [Boeuf, Gilles] Museum Natl Hist Nat, Off President, F-75005 Paris, France. [Jorgensen, Even H.] Univ Tromso, Dept Arctic & Marine Biol, N-9037 Tromso, Norway. [Mazan, Sylvie] CNRS, Stn Biol Roscoff, Unite Mixte Rech 7150, F-29680 Roscoff, France. [Hyodo, Susumu] Univ Tokyo, Atmosphere & Ocean Res Inst, Chiba 2778564, Japan. RP Klein, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov RI Besseau, Laurence/O-9942-2015 OI Besseau, Laurence/0000-0002-9617-8190 FU French Research National Agency [07-BLAN-0097-01]; Centre National de la Recherche Scientifique, Institut francais de recherche pour l'exploitation de la mer and Universite Pierre et Marie Curie-Paris 6 [GDR2821, UMR7232]; Japan Society for the Promotion of Science; intramural programs of the National Institute of Child Health and Human Development; National Library of Medicine; Center for Information Technology FX We want to thank J. A. Donald, T. Toop, and J. D. Bell for assistance in providing specimens of C. milii and also M. Gabriel Diaz (fisherman in Port-Vendres, France) for providing the S. canicula individuals. This study was supported by French Research National Agency Grant 07-BLAN-0097-01, the Centre National de la Recherche Scientifique, Institut francais de recherche pour l'exploitation de la mer and Universite Pierre et Marie Curie-Paris 6 Grants GDR2821 and UMR7232, the Japan Society for the Promotion of Science, and the intramural programs of the National Institute of Child Health and Human Development, the National Library of Medicine, and the Center for Information Technology (all at the National Institutes of Health). NR 51 TC 20 Z9 20 U1 2 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 2014 VL 111 IS 1 BP 314 EP 319 DI 10.1073/pnas.1312634110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700082 PM 24351931 ER PT J AU Janelsins, BM Lu, MF Datta, SK AF Janelsins, Brian M. Lu, Mingfang Datta, Sandip K. TI Altered inactivation of commensal LPS due to acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T cell polarization; gut immunity; endotoxin tolerance; oral immunization; Toll-like receptor ID LAMINA PROPRIA; T-CELLS; RETINOIC ACID; BACTERIAL LIPOPOLYSACCHARIDE; ENDOTOXIN TOLERANCE; SMALL-INTESTINE; DIFFERENTIATION; MICROBIOTA; DISEASE; T(H)17 AB Interleukin (IL) 17-secreting CD4(+) helper T cells (Th17 cells) are essential for host defense at mucosal surfaces, and Th17 cell dysregulation can result in autoimmunity. Exposure to microbial products, such as bacterial LPS, can affect the ability of dendritic cells (DCs) to polarize Th17 cells. Acyloxyacyl hydrolase (AOAH) is a mammalian enzyme expressed by antigen (Ag)-presenting cells that deacylates and thereby inactivates LPS in host tissues. We hypothesized that inactivation of intestinal microbiota-derived LPS by AOAH influences the ability of DCs to polarize and generate Th17 effector cells. We found that LPS-containing Gram-negative microbiota augmented the differentiation of Ag-specific Th17 cells, and identified a colonic DC subset (CD103(+)CD11b(+)ALDH(-)) displaying a unique capacity to both express AOAH and polarize Th17 cells. Compared with WT, these Aoah(-/-) colonic DCs produce less IL-6, resulting in diminished Ag-specific Th17 polarization and increased regulatory T-cell induction in vitro. Oral administration of LPS led to reduced IL-6 production from CD103(+) CD11b(+) ALDHcolonic DCs in Aoah(-/-) mice compared with Aoah(+/+) mice, resulting in an abrogated Ag-specific Th17 response in the colon after mucosal immunization that could be rescued by systemic delivery of recombinant IL-6. These data identify the ability of AOAH to modulate microbiota signals that drive Th17 polarization and influence mucosal T-cell immunity, and suggest that host pathways to handle microbiota-derived products may be targeted to modulate Th17 responses in the context of inflammatory disorders or infection at mucosal surfaces. C1 [Janelsins, Brian M.; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Lu, Mingfang] NIAID, Antibacterial Host Def Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Datta, SK (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dattas@niaid.nih.gov OI Datta, Sandip/0000-0003-0243-7815 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank R. Munford for a critical reading of the manuscript. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 47 TC 14 Z9 14 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 2014 VL 111 IS 1 BP 373 EP 378 DI 10.1073/pnas.1311987111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700092 PM 24344308 ER PT J AU Hara, Y Yuk, F Puri, R Janssen, WGM Rapp, PR Morrison, JH AF Hara, Yuko Yuk, Frank Puri, Rishi Janssen, William G. M. Rapp, Peter R. Morrison, John H. TI Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE toroidal mitochondria; axonal bouton; cognition ID ALZHEIMERS-DISEASE; RHESUS-MONKEYS; COGNITIVE DECLINE; GLUCOSE-METABOLISM; NONHUMAN-PRIMATES; OXIDATIVE STRESS; RECEPTOR-BETA; AGING BRAIN; MENOPAUSE; AGE AB Humans and nonhuman primates are vulnerable to age-and menopause-related decline in working memory, a cognitive function reliant on the energy-demanding recurrent excitation of neurons within Brodmann's Area 46 of the dorsolateral prefrontal cortex (dlPFC). Here, we tested the hypothesis that the number and morphology (straight, curved, or donut-shaped) of mitochondria in dlPFC presynaptic boutons are altered with aging and menopause in rhesus monkeys (Macaca mulatta) and that these metrics correlate with delayed response (DR) accuracy, a well-characterized measure of dlPFC-dependent working memory. Although presynaptic bouton density or size was not significantly different across groups distinguished by age or menses status, DR accuracy correlated positively with the number of total and straight mitochondria per dlPFC bouton. In contrast, DR accuracy correlated inversely with the frequency of boutons containing donut-shaped mitochondria, which exhibited smaller active zone areas and fewer docked synaptic vesicles than those with straight or curved mitochondria. We then examined the effects of estrogen administration to test whether a treatment known to improve working memory influences mitochondrial morphology. Aged ovariectomized monkeys treated with vehicle displayed significant working memory impairment and a concomitant 44% increase in presynaptic donut-shaped mitochondria, both of which were reversed with cyclic estradiol treatment. Together, our data suggest that hormone replacement therapy may benefit cognitive aging, in part by promoting mitochondrial and synaptic health in the dlPFC. C1 [Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G. M.; Morrison, John H.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G. M.; Morrison, John H.] Icahn Sch Med Mt Sinai, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. [Yuk, Frank; Puri, Rishi; Janssen, William G. M.; Morrison, John H.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Morrison, John H.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Morrison, John H.] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. [Rapp, Peter R.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. RP Morrison, JH (reprint author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. EM John.Morrison@mssm.edu RI Hara, Yuko/B-9172-2012 OI Hara, Yuko/0000-0001-5828-442X FU National Institute on Aging [R37 AG06647, R01 AG010606, P01 AG16765]; National Institute on Aging FX We thank Mary Roberts, Sania Fong, Deborah Kent, Katie Hartley, Sona Santos, Heather McKay, and Anne Canfield at the California National Primate Research Center for their expert technical assistance involving the rhesus monkeys; Dr. Donald Canfield for veterinary support; Susan Fink, Ginelle Andrews, and Shannon Wadsworth for expert technical assistance in tissue processing; and Dr. Gareth John for helpful comments on the manuscript. This work was supported by National Institute on Aging Grants R37 AG06647, R01 AG010606, and P01 AG16765 (to J. H. M.), and in part by the Intramural Research Program of the National Institute on Aging. NR 56 TC 37 Z9 37 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 2014 VL 111 IS 1 BP 486 EP 491 DI 10.1073/pnas.1311310110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700111 PM 24297907 ER PT J AU Fok, WC Chen, YD Bokov, A Zhang, YQ Salmon, AB Diaz, V Javors, M Wood, WH Zhang, YQ Becker, KG Perez, VI Richardson, A AF Fok, Wilson C. Chen, Yidong Bokov, Alex Zhang, Yiqiang Salmon, Adam B. Diaz, Vivian Javors, Martin Wood, William H., III Zhang, Yongqing Becker, Kevin G. Perez, Viviana I. Richardson, Arlan TI Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome SO PLOS ONE LA English DT Article ID GENETICALLY HETEROGENEOUS MICE; INDUCED INSULIN-RESISTANCE; LARGE GENE LISTS; GROWTH-FACTOR; C-ELEGANS; DIETARY RESTRICTION; PROTEIN-SYNTHESIS; MAMMALIAN TARGET; OXIDATIVE STRESS; DOWN-REGULATION AB Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity. C1 [Fok, Wilson C.; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Bokov, Alex; Zhang, Yiqiang; Salmon, Adam B.; Diaz, Vivian; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Chen, Yidong; Bokov, Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Zhang, Yiqiang] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Wood, William H., III; Zhang, Yongqing; Becker, Kevin G.] NIA, Baltimore, MD 21224 USA. [Perez, Viviana I.] Oregon State Univ, Dept Biochem & Biophys, Linus Pauling Inst, Corvallis, OR 97331 USA. [Salmon, Adam B.; Richardson, Arlan] Audie Murphy VA Hosp STVHCS, Res Serv, San Antonio, TX USA. [Salmon, Adam B.; Richardson, Arlan] Audie Murphy VA Hosp STVHCS, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu OI Fok, Wilson Chun Yim/0000-0003-3289-2093; Salmon, Adam/0000-0002-1475-7843; Becker, Kevin/0000-0002-6794-6656 FU San Antonio Nathan Shock Aging Center [1p30-AG-13319]; National Institutes of Health (NIH) [AG036613, AG021890]; Ellison Medical Foundation; Intramural Research Program of the NIH, National Institute on Aging; VA Merit grant from the Department of Veteran Affairs; National Institute on Minority Health and Health Disparities from the NIH [G12MD007591] FX Financial support was provided by The San Antonio Nathan Shock Aging Center (1p30-AG-13319, AR), National Institutes of Health (NIH) RC2 Grand Opportunity grant (AG036613, AR), NIH T32 Training Grant (AG021890, WF), the Ellison Medical Foundation (VP), the Intramural Research Program of the NIH, National Institute on Aging, and VA Merit grant (Richardson) from the Department of Veteran Affairs. Computation Support was provided by the Computational System Biology Core funded by the National Institute on Minority Health and Health Disparities (G12MD007591) from the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 37 Z9 38 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 7 PY 2014 VL 9 IS 1 AR e83988 DI 10.1371/journal.pone.0083988 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286JC UT WOS:000329463500013 PM 24409289 ER PT J AU Braganza, MZ Rajaraman, P Park, Y Inskip, PD Freedman, ND Hollenbeck, AR de Gonzalez, AB Kitahara, CM AF Braganza, M. Z. Rajaraman, P. Park, Y. Inskip, P. D. Freedman, N. D. Hollenbeck, A. R. de Gonzalez, A. Berrington Kitahara, C. M. TI Cigarette smoking, alcohol intake, and risk of glioma in the NIH-AARP Diet and Health Study SO BRITISH JOURNAL OF CANCER LA English DT Article DE brain cancer; smoking; alcohol; glioma; prospective cohort study; epidemiology ID BRAIN-TUMOR-EPIDEMIOLOGY; LOS-ANGELES-COUNTY; ADULT-ONSET GLIOMA; LIFE-STYLE FACTORS; UNITED-STATES; CANCER RISK; COHORT; WOMEN; CONSUMPTION; METAANALYSIS AB Background: Although cigarette smoking and alcohol drinking increase the risk of several cancers and certain components of cigarette smoke and alcohol can penetrate the blood-brain barrier, it remains unclear whether these exposures influence the risk of glioma. Methods: We examined the associations between cigarette smoking, alcohol intake, and risk of glioma in the National Institutes of Health-AARP Diet and Health Study, a prospective study of 477 095 US men and women ages 50-71 years at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using models with age as the time metric and adjusted for sex, race/ethnicity, education, and marital status. Results: During a median 10.5 person-years of follow-up, 492 men and 212 women were diagnosed with first primary glioma. Among men, current, heavier smoking was associated with a reduced risk of glioma compared with never smoking, but this was based on only nine cases. No associations were observed between smoking behaviours and glioma risk in women. Greater alcohol consumption was associated with a decreased risk of glioma, particularly among men (>2 drinks per day vs <1 drink per week: HR = 0.67, 95% CI = 0.51-0.90). Conclusion: Smoking and alcohol drinking do not appear to increase the risk of glioma. C1 [Braganza, M. Z.; Rajaraman, P.; Park, Y.; Inskip, P. D.; Freedman, N. D.; de Gonzalez, A. Berrington; Kitahara, C. M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hollenbeck, A. R.] AARP, AARP Res, Washington, DC 20049 USA. RP Braganza, MZ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM melissa.braganza@nih.gov RI Freedman, Neal/B-9741-2015; Kitahara, Cari/R-8267-2016; OI Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 39 TC 10 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 7 PY 2014 VL 110 IS 1 BP 242 EP 248 DI 10.1038/bjc.2013.611 PG 7 WC Oncology SC Oncology GA 286UH UT WOS:000329493700030 PM 24335921 ER PT J AU Roberts, LD Bostrom, P O'Sullivan, JF Schinzel, RT Lewis, GD Dejam, A Lee, YK Palma, MJ Calhoun, S Georgiadi, A Chen, MH Ramachandran, VS Larson, MG Bouchard, C Rankinen, T Souza, AL Clish, CB Wang, TJ Estall, JL Soukas, AA Cowan, CA Spiegelman, BM Gerszten, RE AF Roberts, Lee D. Bostrom, Pontus O'Sullivan, John F. Schinzel, Robert T. Lewis, Gregory D. Dejam, Andre Lee, Youn-Kyoung Palma, Melinda J. Calhoun, Sondra Georgiadi, Anastasia Chen, Ming-Huei Ramachandran, Vasan S. Larson, Martin G. Bouchard, Claude Rankinen, Tuomo Souza, Amanda L. Clish, Clary B. Wang, Thomas J. Estall, Jennifer L. Soukas, Alexander A. Cowan, Chad A. Spiegelman, Bruce M. Gerszten, Robert E. TI beta-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic beta-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors SO CELL METABOLISM LA English DT Article ID MITOCHONDRIAL UNCOUPLING PROTEIN; GENOME-WIDE ASSOCIATION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; INSULIN-RESISTANCE; COACTIVATOR PGC-1; GENE-EXPRESSION; LIVER-DISEASE; PPAR-ALPHA; IN-VIVO AB The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1 alpha transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1 alpha-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1 alpha, and identified beta-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and beta-oxidation in hepatocytes both in vitro and in vivo through a PPAR alpha-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases. C1 [Roberts, Lee D.; O'Sullivan, John F.; Schinzel, Robert T.; Lewis, Gregory D.; Dejam, Andre; Lee, Youn-Kyoung; Palma, Melinda J.; Wang, Thomas J.; Cowan, Chad A.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Bostrom, Pontus; Calhoun, Sondra; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bostrom, Pontus; Calhoun, Sondra; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bostrom, Pontus; Georgiadi, Anastasia] Karolinska Inst, Inst Cell Och Mol Biol CMB, S-17177 Stockholm, Sweden. [Schinzel, Robert T.; Lee, Youn-Kyoung; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Schinzel, Robert T.; Lee, Youn-Kyoung; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Schinzel, Robert T.] Free Univ Berlin, Fachbereich Biol, Inst Biotechnol Mikrobiol, D-14195 Berlin, Germany. [Lewis, Gregory D.; Wang, Thomas J.; Cowan, Chad A.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Lewis, Gregory D.; Souza, Amanda L.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Chen, Ming-Huei; Ramachandran, Vasan S.; Larson, Martin G.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Chen, Ming-Huei; Ramachandran, Vasan S.; Larson, Martin G.] Boston Univ, Sch Med, Framingham, MA 01702 USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Ming-Huei] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiol, Nashville, TN 37232 USA. [Estall, Jennifer L.] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. [Soukas, Alexander A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gerszten, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM rgerszten@partners.org RI Bouchard, Claude/A-7637-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Roberts, Lee/0000-0002-1455-5248 FU NIH [R01 DK081572, R01 HL098280, DK 31405]; Leducq Foundation; American Heart Association; NIH/NHLBI [N01-HC-25195]; Leducq Foundation Career Development Award; Wenner-Gren Foundation; Swedish Heart and Lung Foundation; John W. Barton Sr. Chair in Genetics and Nutrition; [NIH-RO1-HL045670] FX This work was supported by NIH R01 DK081572, NIH R01 HL098280, the Leducq Foundation, and the American Heart Association (R.E.G.) and by NIH DK 31405 (B.M.S.). The Framingham Heart Study is supported by NIH/NHLBI N01-HC-25195. L.D.R. is supported by a Leducq Foundation Career Development Award. P.B. is supported by the Wenner-Gren Foundation and the Swedish Heart and Lung Foundation. The HERITAGE Family Study is supported by NIH-RO1-HL045670. C.B. is supported by the John W. Barton Sr. Chair in Genetics and Nutrition. NR 56 TC 103 Z9 105 U1 5 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 7 PY 2014 VL 19 IS 1 BP 96 EP 108 DI 10.1016/j.cmet.2013.12.003 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 285YO UT WOS:000329431200012 PM 24411942 ER PT J AU Franceschini, N Haack, K Almasy, L Laston, S Lee, ET Best, LG Fabsitz, RR MacCluer, JW Howard, BV Umans, JG Cole, SA AF Franceschini, Nora Haack, Karin Almasy, Laura Laston, Sandra Lee, Elisa T. Best, Lyle G. Fabsitz, Richard R. MacCluer, Jean W. Howard, Barbara V. Umans, Jason G. Cole, Shelley A. TI Generalization of Associations of Kidney-Related Genetic Loci to American Indians SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; STRONG HEART FAMILY; LINKAGE ANALYSIS; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; SERUM CREATININE; APOL1 VARIANTS; RISK-FACTORS; ALBUMINURIA AB Background and objectivesCKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown.Design, setting, participants, & measurementsThis study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used.ResultsThis study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 x 10(-3) to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians.ConclusionThis study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries. C1 [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Haack, Karin; Almasy, Laura; Laston, Sandra; MacCluer, Jean W.; Cole, Shelley A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Howard, Barbara V.; Umans, Jason G.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Umans, Jason G.] Georgetown & Howard Univ Ctr Clin & Translat Sci, Washington, DC USA. RP Franceschini, N (reprint author), Univ N Carolina, 137 East Franklin St, Suite 306 CB 8050, Chapel Hill, NC 27599 USA. EM noraf@unc.edu FU National Heart, Lung, and Blood Institute [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]; American Heart Association [0675001N]; National Center for Research Resources [C06 RR013556] FX The Strong Heart Study is supported by National Heart, Lung, and Blood Institute Grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521. Funding for genotyping was obtained through American Heart Association Grant 0675001N. This study was conducted in part by facility improvements funded by National Center for Research Resources Grant C06 RR013556. NR 42 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN 7 PY 2014 VL 9 IS 1 BP 150 EP 158 DI 10.2215/CJN.02300213 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 285AL UT WOS:000329364700021 PM 24311711 ER PT J AU Yoshimura, T Galligan, C Takahashi, M Chen, KQ Liu, MY Tessarollo, L Wang, JM AF Yoshimura, Teizo Galligan, Carole Takahashi, Munehisa Chen, Keqiang Liu, Mingyong Tessarollo, Lino Wang, Ji Ming TI Non-myeloid cells are major contributors to innate immune responses via production of monocyte chemoattractant protein-1/CCL2 SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE chemokines; inflammation; innate immunity; myeloid cells; gene knockout mice ID NEUTROPHIL ATTRACTANT PROTEIN-1; CHEMOKINE RECEPTORS; MACROPHAGES; LIPOPOLYSACCHARIDE; INFLAMMATION; EXPRESSION; ARTHRITIS; DISEASE; ROLES; MCP-1 AB Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine regulating the recruitment of monocytes into sites of inflammation and cancer. MCP-1 can be produced by a variety of cell types, such as macrophages, neutrophils, fibroblasts, endothelial cells, and epithelial cells. Notably, macrophages produce high levels of MCP-1 in response to proinflammatory stimuli in vitro, leading to the hypothesis that macrophages are the major source of MCP-1 during inflammatory responses in vivo. In stark contrast to the hypothesis, however, there was no significant reduction in MCP-1 protein or the number of infiltrating macrophages in the peritoneal inflammatory exudates of myeloid cell-specific MCP-1-deficient mice in response to i.p injection of thioglycollate or zymosan A. Furthermore, injection of LPS into skin air pouch also had no effect on local MCP-1 production in myeloid-specific MCP-1-deficient mice. Finally, myeloid-specific MCP-1-deficiency did not reduce MCP-1 mRNA expression or macrophage infiltration in LPS-induced lung injury. These results indicate that non-myeloid cells, in response to a variety of stimulants, play a previously unappreciated role in innate immune responses as the primary source of MCP-1. C1 [Yoshimura, Teizo; Galligan, Carole; Takahashi, Munehisa; Chen, Keqiang; Liu, Mingyong; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Bldg 559,Room 2,POB B, Frederick, MD 21702 USA. EM yoshimut@mail.nih.gov FU Intramural Research Program of the NIH; NCI; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We are grateful to Steven Stull, Timothy Back, and staff of LASP, SAIC-Frederick, Inc., for their assistance in animal studies. We are also grateful to Dr. Joost J. Oppenheim for his critical comments. This research was supported by the Intramural Research Program of the NIH, NCI, and National Cancer Institute, National Institutes of Health Contract HHSN261200800001E. NR 29 TC 2 Z9 2 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD JAN 7 PY 2014 VL 4 AR 482 DI 10.3389/fimmu.2013.00482 PG 6 WC Immunology SC Immunology GA CH4VI UT WOS:000354030900001 PM 24432017 ER PT J AU Li, D Jin, CF Jiao, XD Li, L Bushra, T Naeem, MA Butt, NH Husnain, T Sieving, PA Riazuddin, S Riazuddin, SA Hejtmancik, JF AF Li, David Jin, Chongfei Jiao, Xiaodong Li, Lin Bushra, Tahmina Naeem, Muhammad Asif Butt, Nadeem H. Husnain, Tayyab Sieving, Paul A. Riazuddin, Sheikh Riazuddin, S. Amer Hejtmancik, J. Fielding TI AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration SO MOLECULAR VISION LA English DT Article ID LEBER CONGENITAL AMAUROSIS; CONSANGUINEOUS PAKISTANI FAMILIES; CONE DYSTROPHY CORD5; RETINITIS-PIGMENTOSA; CGMP PHOSPHODIESTERASE; ROD PHOSPHODIESTERASE; GENE-MUTATIONS; PHOTORECEPTORS; SUBUNIT; PROTEIN AB Purpose: To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Methods: Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. Results: Genome-wide linkage scans yielded a lod score of 3.05 at theta=0 for D17S1832 and 3.82 at theta=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Conclusions: The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families. C1 [Li, David; Jin, Chongfei; Jiao, Xiaodong; Li, Lin; Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Jin, Chongfei] Zhejiang Univ, Coll Med, Affiliated Hosp 2, Ctr Eye, Hangzhou 310003, Zhejiang, Peoples R China. [Bushra, Tahmina; Naeem, Muhammad Asif; Husnain, Tayyab; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Butt, Nadeem H.; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Hejtmancik, JF (reprint author), NEI, MOGS, OGVFB, NIH, 5635 Fishers Lane,Room 1127, Rockville, MD 20852 USA. EM f3h@helix.nih.gov RI Husnain, Tayyab/G-3805-2015 FU Higher Education Commission; NEI [EY000272]; Ministry of Science and Technology Islamabad, Pakistan FX The authors are thankful to all family members for their participation in this study. The authors are grateful to the staff of Layton Rehmatullah Benevolent Trust (LRBT) Hospital for clinical evaluation of affected individuals. This study was supported, in part by Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan and by NEI EY000272. NR 47 TC 5 Z9 5 U1 0 U2 3 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JAN 6 PY 2014 VL 20 BP 1 EP 14 PG 14 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA AB5JM UT WOS:000331824700001 PM 24426771 ER PT J AU Berrigan, D Tatalovich, Z Pickle, LW Ewing, R Ballard-Barbash, R AF Berrigan, David Tatalovich, Zaria Pickle, Linda W. Ewing, Reid Ballard-Barbash, Rachel TI Urban sprawl, obesity, and cancer mortality in the United States: cross-sectional analysis and methodological challenges SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article DE Urban sprawl; Cancer mortality; Obesity; Spatial heterogeneity; Census division; County; Health disparities; Ecological analysis ID BODY-MASS INDEX; PHYSICAL-ACTIVITY LEVELS; COUNTY-LEVEL PREVALENCE; BUILT ENVIRONMENT; POPULATION-DENSITY; SUBURBAN SPRAWL; RISK-FACTORS; LUNG-CANCER; HEALTH; EPIDEMIOLOGY AB Background: Urban sprawl has the potential to influence cancer mortality via direct and indirect effects on obesity, access to health services, physical activity, transportation choices and other correlates of sprawl and urbanization. Methods: This paper presents a cross-sectional analysis of associations between urban sprawl and cancer mortality in urban and suburban counties of the United States. This ecological analysis was designed to examine whether urban sprawl is associated with total and obesity-related cancer mortality and to what extent these associations differed in different regions of the US. A major focus of our analyses was to adequately account for spatial heterogeneity in mortality. Therefore, we fit a series of regression models, stratified by gender, successively testing for the presence of spatial heterogeneity. Our resulting models included county level variables related to race, smoking, obesity, access to health services, insurance status, socioeconomic position, and broad geographic region as well as a measure of urban sprawl and several interactions. Our most complex models also included random effects to account for any county-level spatial autocorrelation that remained unexplained by these variables. Results: Total cancer mortality rates were higher in less sprawling areas and contrary to our initial hypothesis; this was also true of obesity related cancers in six of seven U.S. regions (census divisions) where there were statistically significant associations between the sprawl index and mortality. We also found significant interactions (p < 0.05) between region and urban sprawl for total and obesity related cancer mortality in both sexes. Thus, the association between urban sprawl and cancer mortality differs in different regions of the US. Conclusions: Despite higher levels of obesity in more sprawling counties in the US, mortality from obesity related cancer was not greater in such counties. Identification of disparities in cancer mortality within and between geographic regions is an ongoing public health challenge and an opportunity for further analytical work identifying potential causes of these disparities. Future analyses of urban sprawl and health outcomes should consider exploring regional and international variation in associations between sprawl and health. C1 [Berrigan, David; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Tatalovich, Zaria] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Pickle, Linda W.] StatNet Consulting, Gaithersburg, MD 20879 USA. [Ewing, Reid] Univ Utah, Coll Architecture & Planning, Salt Lake City, UT 84112 USA. RP Berrigan, D (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM berrigad@mail.nih.gov NR 74 TC 10 Z9 10 U1 4 U2 33 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD JAN 6 PY 2014 VL 13 AR 3 DI 10.1186/1476-072X-13-3 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297UH UT WOS:000330280000001 PM 24393615 ER PT J AU Ferreira, NC Marques, IA Conceicao, WA Macedo, B Machado, CS Mascarello, A Chiaradia-Delatorre, LD Yunes, RA Nunes, RJ Hughson, AG Raymond, LD Pascutti, PG Caughey, B Cordeiro, Y AF Ferreira, Natalia C. Marques, Icaro A. Conceicao, Wesley A. Macedo, Bruno Machado, Clarice S. Mascarello, Alessandra Chiaradia-Delatorre, Louise Domeneghini Yunes, Rosendo Augusto Nunes, Ricardo Jose Hughson, Andrew G. Raymond, Lynne D. Pascutti, Pedro G. Caughey, Byron Cordeiro, Yraima TI Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: In Vitro and In Silico Approaches SO PLOS ONE LA English DT Article ID QUINOLINE DERIVATIVES; ANTIPRION ACTIVITY; NUCLEIC-ACIDS; PROTEIN; DISEASE; INHIBITORS; SCRAPIE; AGGREGATION; CHALCONES; QUINACRINE AB The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrPC) into the scrapie form (PrPSc) is the hallmark of TSEs. Once formed, PrPSc aggregates and catalyzes PrPC misfolding into new PrPSc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed in vivo due to poor pharmacokinetic profiles. In this work we propose a combined in vitro/in silico approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrPSc (ScN2a) for their ability to inhibit PK-resistant PrP (PrPRes) accumulation. From,200 compounds, 47 were effective in decreasing the accumulation of PrPRes in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted in silico, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrPRes from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP109-149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined in vitro/in silico approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrPRes in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy. C1 [Ferreira, Natalia C.; Marques, Icaro A.; Conceicao, Wesley A.; Macedo, Bruno; Machado, Clarice S.; Cordeiro, Yraima] Univ Fed Rio de Janeiro, Fac Farm, Rio De Janeiro, Brazil. [Conceicao, Wesley A.; Pascutti, Pedro G.] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil. [Mascarello, Alessandra; Chiaradia-Delatorre, Louise Domeneghini; Yunes, Rosendo Augusto; Nunes, Ricardo Jose] Univ Fed Santa Catarina, Dept Quim, Florianopolis, SC, Brazil. [Hughson, Andrew G.; Raymond, Lynne D.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Cordeiro, Y (reprint author), Univ Fed Rio de Janeiro, Fac Farm, Rio De Janeiro, Brazil. EM yraima@pharma.ufrj.br RI Cordeiro, Yraima/J-7619-2012 OI Cordeiro, Yraima/0000-0003-4278-212X FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Instituto Nacional de Ciencia e Tecnologia de Biologia Estrutural e Bioimagem (INBEB); Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) from Brazil; Intramural Research Program of the NIAID, NIH, USA FX This work was supported by grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), from the Instituto Nacional de Ciencia e Tecnologia de Biologia Estrutural e Bioimagem (INBEB), Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) from Brazil, and by the Intramural Research Program of the NIAID, NIH, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 13 Z9 13 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 6 PY 2014 VL 9 IS 1 AR e84531 DI 10.1371/journal.pone.0084531 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700032 PM 24400098 ER PT J AU Knodler, LA Nair, V Steele-Mortimer, O AF Knodler, Leigh A. Nair, Vinod Steele-Mortimer, Olivia TI Quantitative Assessment of Cytosolic Salmonella in Epithelial Cells SO PLOS ONE LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; INTRACELLULAR LIFE-STYLE; SHIGELLA-FLEXNERI; MYCOBACTERIUM-TUBERCULOSIS; CONTAINING VACUOLE; COXIELLA-BURNETII; III SECRETION; PHAGOLYSOSOMAL ALKALINIZATION; FRANCISELLA-TULARENSIS; ESCHERICHIA-COLI AB Within mammalian cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) inhabits a membrane-bound vacuole known as the Salmonella-containing vacuole (SCV). We have recently shown that wild type S. Typhimurium also colonizes the cytosol of epithelial cells. Here we sought to quantify the contribution of cytosolic Salmonella to the total population over a time course of infection in different epithelial cell lines and under conditions of altered vacuolar escape. We found that the lysosomotropic agent, chloroquine, acts on vacuolar, but not cytosolic, Salmonella. After chloroquine treatment, vacuolar bacteria are not transcriptionally active or replicative and appear degraded. Using a chloroquine resistance assay, in addition to digitonin permeabilization, we found that S. Typhimurium lyses its nascent vacuole in numerous epithelial cell lines, albeit with different frequencies, and hyper-replication in the cytosol is also widespread. At later times post-infection, cytosolic bacteria account for half of the total population in some epithelial cell lines, namely HeLa and Caco-2 C2Bbe1. Both techniques accurately measured increased vacuole lysis in epithelial cells upon treatment with wortmannin. By chloroquine resistance assay, we also determined that Salmonella pathogenicity island-1 (SPI-1), but not SPI-2, the virulence plasmid nor the flagellar apparatus, was required for vacuolar escape and cytosolic replication in epithelial cells. Together, digitonin permeabilization and the chloroquine resistance assay will be useful, complementary tools for deciphering the mechanisms of SCV lysis and Salmonella replication in the epithelial cell cytosol. C1 [Knodler, Leigh A.] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. [Knodler, Leigh A.; Steele-Mortimer, Olivia] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. [Nair, Vinod] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Knodler, LA (reprint author), Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. EM lknodler@vetmed.wsu.edu FU Paul G. Allen School for Global Animal Health; Stanley L. Adler Research Endowment; Intramural Research Program of NIAID FX This work is supported by the Paul G. Allen School for Global Animal Health, the Stanley L. Adler Research Endowment and the Intramural Research Program of NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 22 Z9 22 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 6 PY 2014 VL 9 IS 1 AR e84681 DI 10.1371/journal.pone.0084681 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700042 PM 24400108 ER PT J AU Lin, RS Jimenez-Movilla, M Dean, J AF Lin, Ruei-Shiuan Jimenez-Movilla, Maria Dean, Jurrien TI Figla-Cre Transgenic Mice Expressing Myristoylated EGFP in Germ Cells Provide a Model for Investigating Perinatal Oocyte Dynamics SO PLOS ONE LA English DT Article ID TRANSCRIPTION FACTOR; PRIMORDIAL FOLLICLES; GENE-EXPRESSION; UNDIFFERENTIATED SPERMATOGONIA; MEIOTIC PROPHASE; OVARIAN-FOLLICLE; SPERM CHROMATIN; MOUSE OOCYTES; APOPTOSIS; DNA AB FIGLA (Factor in the germline, alpha) is a bHLH transcription factor expressed abundantly in female and less so in male germ cells. Mice lacking FIGLA do not form primordial follicles in the ovary and females are sterile, but there is no obvious phenotype in males. Using the Figla promoter to express Cre recombinase, we have established mEGFP/mTomato reporter mice with green germ cells and red somatic tissue. These mice were crossed into the Figla null background to accelerate perinatal oocyte loss. Live imaging of cultured newborn ovaries provides evidence that few oocytes egress and the vast majority disappear within the confines of the ovary. Although a cohort of mobile, phagocytic cells was observed, macrophage depletion in Csf1(op/op) mice did not affect oocyte loss. Investigations with TUNEL assays and caspase inhibitors suggest that apoptosis plays a role in the perinatal loss of oocyte in female mice. These results establish the utility of Figla-EGFP/Cre; mTomato/mEGFP in investigating germ cell dynamics in prepubertal mice. C1 [Lin, Ruei-Shiuan; Jimenez-Movilla, Maria; Dean, Jurrien] Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA. RP Dean, J (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA. EM jurriend@helix.nih.gov RI Jimenez-Movilla, Maria/I-1004-2015 OI Jimenez-Movilla, Maria/0000-0002-1572-8219 FU Intramural Research Program of the National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 6 Z9 7 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 6 PY 2014 VL 9 IS 1 AR e84477 DI 10.1371/journal.pone.0084477 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700026 PM 24400092 ER PT J AU Zhao, Z Zhong, LL Elrod, E Struble, E Ma, L Yan, HL Harman, C Deng, L Virata-Theimer, ML Liu, P Alter, H Grakoui, A Zhang, P AF Zhao, Zhong Zhong, Lilin Elrod, Elizabeth Struble, Evi Ma, Li Yan, Hailing Harman, Christine Deng, Lu Virata-Theimer, Maria Luisa Liu, Peter Alter, Harvey Grakoui, Arash Zhang, Pei TI A Neutralization Epitope in the Hepatitis C Virus E2 Glycoprotein Interacts with Host Entry Factor CD81 SO PLOS ONE LA English DT Article ID ENVELOPE GLYCOPROTEIN; VIRAL ENTRY; ANTIBODIES; BINDING; PARTICLES; INFECTION; PLASMA; GENOTYPES; RECEPTOR; PROGRESS AB The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design. By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein. We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81. Furthermore, we detected "1H8-like" antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection. The time course study of plasma samples from Patient H, a well-characterized case of post-transfusion hepatitis C, showed that "1H8-like" antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo. The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections. C1 [Zhao, Zhong; Zhong, Lilin; Struble, Evi; Ma, Li; Yan, Hailing; Harman, Christine; Deng, Lu; Virata-Theimer, Maria Luisa; Liu, Peter; Zhang, Pei] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. [Elrod, Elizabeth; Grakoui, Arash] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Alter, Harvey] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov FU Modernizing Science Funds of the Food and Drug Administration FX This study was supported by the Modernizing Science Funds of the Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 4 Z9 4 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 6 PY 2014 VL 9 IS 1 AR e84346 DI 10.1371/journal.pone.0084346 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700018 PM 24400084 ER PT J AU Moissoglu, K Majumdar, R Parent, CA AF Moissoglu, Konstadinos Majumdar, Ritankar Parent, Carole A. TI Cell Migration: Sinking in a Gradient SO CURRENT BIOLOGY LA English DT Editorial Material ID TISSUE MIGRATION; CXCR7; CHEMOTAXIS; GUIDANCE AB How chemoattractant gradients form and persist in complex tissues is a key question in cell migration. Two studies now show that CXCR7 acts as a sink in the migrating zebrafish lateral line primordium to generate SDF1 gradients. C1 [Moissoglu, Konstadinos; Majumdar, Ritankar; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov OI Majumdar, Ritankar/0000-0001-6624-0187 NR 20 TC 6 Z9 6 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 6 PY 2014 VL 24 IS 1 BP R23 EP R25 DI 10.1016/j.cub.2013.10.075 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 286XA UT WOS:000329501400009 PM 24405672 ER PT J AU Bonifacino, JS AF Bonifacino, Juan S. TI Adaptor proteins involved in polarized sorting SO JOURNAL OF CELL BIOLOGY LA English DT Review ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; MANNOSE 6-PHOSPHATE RECEPTORS; PROGRESSIVE SPASTIC PARAPLEGIA; SENSORY ORGAN PRECURSOR; TRANS-GOLGI NETWORK; DARBY CANINE KIDNEY; EPITHELIAL-CELLS; MEMBRANE-PROTEINS; PLASMA-MEMBRANE; MDCK CELLS AB Polarized cells such as epithelial cells and neurons exhibit different plasma membrane domains with distinct protein compositions. Recent studies have shown that sorting of transmembrane proteins to the basolateral domain of epithelial cells and the somatodendritic domain of neurons is mediated by recognition of signals in the cytosolic domains of the proteins by adaptors. These adaptors are components of protein coats associated with the trans-Golgi network and/or recycling endosomes. The clathrin-associated adaptor protein 1 (AP-1) complex plays a preeminent role in this process, although other adaptors and coat proteins, such as AP-4, ARH, Numb, exomer, and retromer, have also been implicated. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM bonifacinoj@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural Program of the National Institute of Child Health and Human Development, National Institutes of Health FX Work in my laboratory is funded by the Intramural Program of the National Institute of Child Health and Human Development, National Institutes of Health. NR 99 TC 60 Z9 60 U1 3 U2 35 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JAN 6 PY 2014 VL 204 IS 1 BP 7 EP 17 DI 10.1083/jcb.201310021 PG 11 WC Cell Biology SC Cell Biology GA 284UR UT WOS:000329347100003 PM 24395635 ER PT J AU Weickert, TW Terrazas, A Bigelow, LB Apud, JA Egan, MF Weinberger, DR AF Weickert, Thomas W. Terrazas, Alejandro Bigelow, Llewellyn B. Apud, Jose A. Egan, Michael F. Weinberger, Daniel R. TI Perceptual category judgment deficits are related to prefrontal decision making abnormalities in schizophrenia SO FRONTIERS IN PSYCHIATRY LA English DT Article DE schizophrenia; perceptual category judgment; prefrontal cortex AB Previous studies of perceptual category learning in patients with schizophrenia generally demonstrate impaired perceptual category learning; however, traditional cognitive studies have often failed to address the relationship of different cortical regions to perceptually based category learning and judgments in healthy participants and patients with schizophrenia. In the present study, perceptual category learning was examined in 26 patients with schizophrenia and 25 healthy participants using a dot-pattern category learning task. In the training phase, distortions of a prototypical dot pattern were presented. In the test phase, participants were shown the prototype, low and high distortions of the prototype, and random dot patterns. Participants were required to indicate whether the presented dot pattern was a member of the category of dot-patterns previously presented during the study phase. Patients with schizophrenia displayed an impaired ability to make judgments regarding marginal members of novel, perceptually based categories relative to healthy participants. Category judgment also showed opposite patterns of strong, significant correlations with behavioral measures of prefrontal cortex function in patients relative to healthy participants. These results suggest that impaired judgments regarding novel, perceptually based category membership may be due to abnormal prefrontal cortex function in patients with schizophrenia. C1 [Weickert, Thomas W.; Terrazas, Alejandro; Bigelow, Llewellyn B.; Apud, Jose A.; Egan, Michael F.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Weickert, Thomas W.] Univ New South Wales, Sch Psychiat, Randwick, NSW, Australia. [Weickert, Thomas W.] Neurosci Res Australia, Randwick, NSW, Australia. [Terrazas, Alejandro] Nielsen, Adv R&D MSci, San Francisco, CA USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. RP Weickert, TW (reprint author), Univ New South Wales, Sch Psychiat, Neurosci Res Australia, Barker St, Randwick, NSW 2031, Australia. EM t.weickert@unsw.edu.au FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health FX The authors would like to thank Karlene Nguyen for preparation of the computer program used in this study, Christine Russo for assistance with neuropsychological data collection, Mei-Hsin Cheng for assistance with data management, Terry Goldberg and Cynthia Shannon Weickert for their comments on earlier versions of this manuscript, and the NIH Warren G. Magnuson Clinical Center nursing staff not only for providing superior quality care to all inpatients participating in this study but also for their routine administration and scoring of the PANSS. This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 71 TC 2 Z9 2 U1 2 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD JAN 6 PY 2014 VL 4 AR 184 DI 10.3389/fpsyt.2013.00184 PG 10 WC Psychiatry SC Psychiatry GA V46QB UT WOS:000209897600001 PM 24432006 ER PT J AU Morita, D Rah, JC Isaac, JTR AF Morita, Daiju Rah, Jong Cheol Isaac, John T. R. TI Incorporation of inwardly rectifying AMPA receptors at silent synapses during hippocampal long-term potentiation SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE glutamate; synaptic plasticity; hippocampus ID SYNAPTIC PLASTICITY; PYRAMIDAL NEURONS; DENDRITIC SPINES; CA1 REGION; LTP; SUBUNIT; TRAFFICKING; INDUCTION; CA2+; ACTIVATION AB Despite decades of study, the mechanisms by which synapses express the increase in strength during long-term potentiation (LTP) remain an area of intense interest. Here, we have studied how AMPA receptor subunit composition changes during the early phases of hippocampal LTP in CA1 pyramidal neurons. We studied LTP at silent synapses that initially lack AMPA receptors, but contain NMDA receptors. We show that strongly inwardly rectifying AMPA receptors are initially incorporated at silent synapses during LTP and are then subsequently replaced by non-rectifying AMPA receptors. These findings suggest that silent synapses initially incorporate GluA2-lacking, calcium-permeable AMPA receptors during LTP that are then replaced by GluA2-containing calcium-impermeable receptors. We also show that LTP consolidation at CA1 synapses requires a rise in intracellular calcium concentration during the early phase of expression, indicating that calcium influx through the GluA2-lacking AMPA receptors drives their replacement by GluA2-containing receptors during LTP consolidation. Taken together with previous studies in hippocampus and in other brain regions, these findings suggest that a common mechanism for the expression of activity-dependent glutamatergic synaptic plasticity involves the regulation of GluA2-subunit composition and highlights a critical role for silent synapses in this process. C1 [Morita, Daiju; Rah, Jong Cheol; Isaac, John T. R.] NINDS, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA. RP Isaac, JTR (reprint author), Eli Lilly & Co, Windlesham GU20 6PH, Surrey, England. EM isaacjo@lilly.com FU NINDS Intramural programme FX This research is supported by the NINDS Intramural programme. NR 38 TC 6 Z9 6 U1 2 U2 6 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 EI 1471-2970 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD JAN 5 PY 2014 VL 369 IS 1633 AR 20130156 DI 10.1098/rstb.2013.0156 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AC4AQ UT WOS:000332463400025 PM 24298157 ER PT J AU Tatem, AJ Campbell, J Guerra-Arias, M de Bernis, L Moran, A Matthews, Z AF Tatem, Andrew J. Campbell, James Guerra-Arias, Maria de Bernis, Luc Moran, Allisyn Matthews, Zoe TI Mapping for maternal and newborn health: the distributions of women of childbearing age, pregnancies and births SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article ID AFRICA; CARE; ACCESSIBILITY; COUNTRIES; SURVIVAL; MALARIA; KENYA; MAPS AB Background: The health and survival of women and their new-born babies in low income countries has been a key priority in public health since the 1990s. However, basic planning data, such as numbers of pregnancies and births, remain difficult to obtain and information is also lacking on geographic access to key services, such as facilities with skilled health workers. For maternal and newborn health and survival, planning for safer births and healthier newborns could be improved by more accurate estimations of the distributions of women of childbearing age. Moreover, subnational estimates of projected future numbers of pregnancies are needed for more effective strategies on human resources and infrastructure, while there is a need to link information on pregnancies to better information on health facilities in districts and regions so that coverage of services can be assessed. Methods: This paper outlines demographic mapping methods based on freely available data for the production of high resolution datasets depicting estimates of numbers of people, women of childbearing age, live births and pregnancies, and distribution of comprehensive EmONC facilities in four large high burden countries: Afghanistan, Bangladesh, Ethiopia and Tanzania. Satellite derived maps of settlements and land cover were constructed and used to redistribute areal census counts to produce detailed maps of the distributions of women of childbearing age. Household survey data, UN statistics and other sources on growth rates, age specific fertility rates, live births, stillbirths and abortions were then integrated to convert the population distribution datasets to gridded estimates of births and pregnancies. Results and conclusions: These estimates, which can be produced for current, past or future years based on standard demographic projections, can provide the basis for strategic intelligence, planning services, and provide denominators for subnational indicators to track progress. The datasets produced are part of national midwifery workforce assessments conducted in collaboration with the respective Ministries of Health and the United Nations Population Fund (UNFPA) to identify disparities between population needs, health infrastructure and workforce supply. The datasets are available to the respective Ministries as part of the UNFPA programme to inform midwifery workforce planning and also publicly available through the WorldPop population mapping project. C1 [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. [Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Campbell, James; Guerra-Arias, Maria] Inst Cooperac Social Integrare, Barcelona, Spain. [de Bernis, Luc] United Nations Populat Fund, Geneva, Switzerland. [Moran, Allisyn] US Agcy Int Dev, Washington, DC 20523 USA. [Matthews, Zoe] Univ Southampton, Dept Social Stat & Demog, Southampton, Hants, England. RP Tatem, AJ (reprint author), Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. EM A.J.Tatem@soton.ac.uk FU NIAID NIH HHS [U19AI089674] NR 42 TC 15 Z9 15 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD JAN 4 PY 2014 VL 13 AR 2 DI 10.1186/1476-072X-13-2 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD9BH UT WOS:000333559000001 PM 24387010 ER PT J AU Kellman, P Hansen, MS AF Kellman, Peter Hansen, Michael S. TI T1-mapping in the heart: accuracy and precision SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Review DE T1 map; Accuracy; Precision; Reproducibility; ECV; Off-resonance; MOLLI; SASHA; ShMOLLI; Cardiovascular magnetic resonance ID CARDIOVASCULAR MAGNETIC-RESONANCE; EXTRACELLULAR VOLUME FRACTION; ACUTE MYOCARDIAL-INFARCTION; INVERSION-RECOVERY MOLLI; GADOPENTETATE DIMEGLUMINE; DILATED CARDIOMYOPATHY; PARTITION-COEFFICIENT; MOTION CORRECTION; CONTRAST T1; IN-VITRO AB The longitudinal relaxation time constant (T1) of the myocardium is altered in various disease states due to increased water content or other changes to the local molecular environment. Changes in both native T1 and T1 following administration of gadolinium (Gd) based contrast agents are considered important biomarkers and multiple methods have been suggested for quantifying myocardial T1 in vivo. Characterization of the native T1 of myocardial tissue may be used to detect and assess various cardiomyopathies while measurement of T1 with extracellular Gd based contrast agents provides additional information about the extracellular volume (ECV) fraction. The latter is particularly valuable for more diffuse diseases that are more challenging to detect using conventional late gadolinium enhancement (LGE). Both T1 and ECV measures have been shown to have important prognostic significance. T1-mapping has the potential to detect and quantify diffuse fibrosis at an early stage provided that the measurements have adequate reproducibility. Inversion recovery methods such as MOLLI have excellent precision and are highly reproducible when using tightly controlled protocols. The MOLLI method is widely available and is relatively mature. The accuracy of inversion recovery techniques is affected significantly by magnetization transfer (MT). Despite this, the estimate of apparent T1 using inversion recovery is a sensitive measure, which has been demonstrated to be a useful tool in characterizing tissue and discriminating disease. Saturation recovery methods have the potential to provide a more accurate measurement of T1 that is less sensitive to MT as well as other factors. Saturation recovery techniques are, however, noisier and somewhat more artifact prone and have not demonstrated the same level of reproducibility at this point in time. This review article focuses on the technical aspects of key T1-mapping methods and imaging protocols and describes their limitations including the factors that influence their accuracy, precision, and reproducibility. C1 [Kellman, Peter; Hansen, Michael S.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM kellman@nih.gov RI Hansen, Michael/J-5391-2015 OI Hansen, Michael/0000-0002-8087-8731 NR 56 TC 114 Z9 119 U1 6 U2 36 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD JAN 4 PY 2014 VL 16 AR 2 DI 10.1186/1532-429X-16-2 PG 20 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AB7VC UT WOS:000331998000001 PM 24387626 ER PT J AU Ma, JJ Shi, YB AF Ma, Jianjie Shi, Yun-Bo TI The Mesobuthus martensii genome reveals the molecular diversity of scorpion toxins SO CELL AND BIOSCIENCE LA English DT Article DE Scorpion; Mesobuthus martensii; Neurotoxin; Genome; Evolution ID TRANSCRIPTOME ANALYSIS; VENOM PEPTIDES; EVOLUTION; COMPONENTS; CHANNEL AB Recent complete sequencing of the genome of the Asian scorpion, Mesobuthus martensii, highlights the molecular diversity of its venom neurotoxin/defensin genes and interesting features of their evolution. C1 [Ma, Jianjie] Ohio State Univ, Wexner Med Ctr, Dept Surg, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA. RP Ma, JJ (reprint author), Ohio State Univ, Wexner Med Ctr, Dept Surg, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. EM Jianjie.Ma@osumc.edu; shi@helix.nih.gov FU National Institutes of Health (NIH); Intramural Research Program of NICHD, NIH FX JM was supported by extramural research grants from the National Institutes of Health (NIH) and YBS was supported by the Intramural Research Program of NICHD, NIH. NR 12 TC 2 Z9 2 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2045-3701 J9 CELL BIOSCI JI Cell Biosci. PD JAN 3 PY 2014 VL 4 AR 1 DI 10.1186/2045-3701-4-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AB7LC UT WOS:000331970500001 PM 24383941 ER PT J AU Kim, C Kim, W Lee, H Ji, E Choe, YJ Martindale, JL Akamatsu, W Okano, H Kim, HS Nam, SW Gorospe, M Lee, EK AF Kim, Chongtae Kim, Wook Lee, Heejin Ji, Eunbyul Choe, Yun-Jeong Martindale, Jennifer L. Akamatsu, Wado Okano, Hideyuki Kim, Ho-Shik Nam, Suk Woo Gorospe, Myriam Lee, Eun Kyung TI The RNA-binding Protein HuD Regulates Autophagosome Formation in Pancreatic beta Cells by Promoting Autophagy-related Gene 5 Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Autophagy; RNA-binding Protein; RNA Metabolism; RNA Turnover; RNA-Protein Interaction ID GAP-43 MESSENGER-RNA; EMBRYONIC STEM-CELLS; NERVE GROWTH-FACTOR; PC12 CELLS; POSTTRANSCRIPTIONAL REGULATION; NEURITE OUTGROWTH; TRANSLATION; DISEASE; ELAV; ATG5 AB Tight regulation of autophagy is critical for the fate of pancreatic beta cells. The autophagy protein ATG5 is essential for the formation of autophagosomes by promoting the lipidation of microtubule-associated protein LC3 (light chain 3). However, little is known about the mechanisms that regulate ATG5 expression levels. In this study, we investigated the regulation of ATG5 expression by HuD. The association of HuD with ATG5 mRNA was analyzed by ribonucleoprotein complex immunoprecipitation and biotin pulldown assays. HuD expression levels in pancreatic beta cells were knocked down via siRNA, elevated by overexpression of a HuD-expressing plasmid. The expression levels of HuD, ATG5, LC3, and -actin were determined by Western blot and quantitative RT-PCR analysis. Autophagosome formation was assessed by fluorescence microscopy in GFP-LC3-expressing cells and in pancreatic tissues from WT and HuD-null mice. We identified ATG5 mRNA as a post-transcriptional target of the mammalian RNA-binding protein HuD in pancreatic beta cells. HuD associated with the 3-UTR of the ATG5 mRNA. Modulating HuD abundance did not alter ATG5 mRNA levels, but HuD silencing decreased ATG5 mRNA translation, and, conversely, HuD overexpression enhanced ATG5 mRNA translation. Through its effect on ATG5, HuD contributed to the lipidation of LC3 and the formation of LC3-positive autophagosomes. In keeping with this regulatory paradigm, HuD-null mice displayed lower ATG5 and LC3 levels in pancreatic beta cells. Our results reveal HuD to be an inducer of ATG5 expression and hence a critical regulator of autophagosome formation in pancreatic beta cells. C1 [Kim, Chongtae; Lee, Heejin; Ji, Eunbyul; Choe, Yun-Jeong; Kim, Ho-Shik; Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea. [Nam, Suk Woo] Catholic Univ Korea, Coll Med, Dept Pathol, Seoul 137701, South Korea. [Kim, Wook] Ajou Univ, Dept Mol Sci & Technol, Suwon 443749, South Korea. [Martindale, Jennifer L.; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Akamatsu, Wado; Okano, Hideyuki] Keio Univ, Grad Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan. RP Lee, EK (reprint author), Catholic Univ Korea, Coll Med, Dept Biochem, 222 Banpodaero, Seoul 137701, South Korea. EM leeek@catholic.ac.kr RI Hidokano, Hideyuki/J-5973-2013 FU National Research Foundation of Korea [20110013116, 012M3A9D1054517, 2012R1A1A1041352]; Korean government; Intramural Research Program of NIA, National Institutes of Health FX This work was supported by National Research Foundation of Korea Grants 20110013116 and 012M3A9D1054517 (to E. K. L.) and 2012R1A1A1041352 (to W. K.) funded by the Korean government and by funds from the Intramural Research Program of NIA, National Institutes of Health (to J. L. M. and M. G.). NR 45 TC 5 Z9 5 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 3 PY 2014 VL 289 IS 1 BP 112 EP 121 DI 10.1074/jbc.M113.474700 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 285CN UT WOS:000329370900010 PM 24275661 ER PT J AU Lai, WS Perera, L Hicks, SN Blackshear, PJ AF Lai, Wi S. Perera, Lalith Hicks, Stephanie N. Blackshear, Perry J. TI Mutational and Structural Analysis of the Tandem Zinc Finger Domain of Tristetraprolin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cytokine; Inflammation; RNA-binding Protein; RNA Turnover; RNA-Protein Interaction; Tumor Necrosis Factor (TNF); AU-rich Elements ID AU-RICH ELEMENT; CONTAINING MESSENGER-RNAS; PRIMARY RESPONSE GENE; GENOME-WIDE ANALYSIS; FORCE-FIELD; C-ELEGANS; PROTEINS; FAMILY; SEQUENCE; BINDING AB Tristetraprolin (TTP), the best known member of a class of tandem (R/K)YKTELCX8CX5CX3H zinc finger proteins, can destabilize target mRNAs by first binding to AU-rich elements (AREs) in their 3-untranslated regions (UTRs) and subsequently promoting deadenylation and ultimate destruction of those mRNAs. This study sought to determine the roles of selected amino acids in the RNA binding domain, known as the tandem zinc finger (TZF) domain, in the ability of the full-length protein to bind to AREs within the tumor necrosis factor (TNF) mRNA 3-UTR. Within the CX8C region of the TZF domain, mutation of some of the residues specific to TTP, not found in other members of the TTP protein family, resulted in decreased binding to RNA as well as inhibited mRNA deadenylation and decay. Evaluation of simulation solution models revealed a distinct structure in the second zinc finger of TTP that was induced by the presence of these TTP-specific residues. In addition, mutations within the lead-in sequences preceding the first C of highly conserved residues within the CX5C or CX3H regions or within the linker region between the two fingers also perturbed both RNA binding and the simulation model of the TZF domain in complex with RNA. We conclude that, although the majority of conserved residues within the TZF domain of TTP are required for productive binding, not all residues at sequence-equivalent positions in the two zinc fingers of the TZF domain of TTP are functionally equivalent. C1 [Lai, Wi S.; Hicks, Stephanie N.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Perera, Lalith] NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, F1-13 Bldg 101,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU National Institutes of Health, NIEHS, Division of Intramural Research FX This work was supported by the National Institutes of Health, NIEHS, Division of Intramural Research. NR 48 TC 9 Z9 10 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 3 PY 2014 VL 289 IS 1 BP 565 EP 580 DI 10.1074/jbc.M113.466326 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 285CN UT WOS:000329370900048 PM 24253039 ER PT J AU Singh, S Prasad, NR Kapoor, K Chufan, EE Patel, BA Ambudkar, SV Talele, TT AF Singh, Satyakam Prasad, Nagarajan Rajendra Kapoor, Khyati Chufan, Eduardo E. Patel, Bhargav A. Ambudkar, Suresh V. Talele, Tanaji T. TI Design, Synthesis, and Biological Evaluation of (S)-Valine Thiazole-Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P-Glycoprotein (ABCB1) SO CHEMBIOCHEM LA English DT Article DE ABC transporters; molecular modeling; multidrug resistance; peptide mimics; P-glycoprotein ID MEDIATED MULTIDRUG-RESISTANCE; CYCLOOLIGOMERISATION REACTIONS; SIMULTANEOUS BINDING; DRUG TRANSPORTERS; MAMMALIAN-CELLS; ATPASE ACTIVITY; AMINO-ACIDS; INHIBITORS; REVERSAL; XR9576 AB Multidrug resistance caused by ATP binding cassette transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure in cancer chemotherapy. Previously, selenazole-containing cyclic peptides were reported as P-gp inhibitors and were also used for co-crystallization with mouse P-gp, which has 87% homology to human P-gp. It has been reported that human P-gp can simultaneously accommodate two to three moderately sized molecules at the drug binding pocket. Our in silico analysis, based on the homology model of human P-gp, spurred our efforts to investigate the optimal size of (S)-valine-derived thiazole units that can be accommodated at the drug binding pocket. Towards this goal, we synthesized varying lengths of linear and cyclic derivatives of (S)-valine-derived thiazole units to investigate the optimal size, lipophilicity, and structural form (linear or cyclic) of valine-derived thiazole peptides that can be accommodated in the P-gp binding pocket and affects its activity, previously an unexplored concept. Among these oligomers, lipophilic linear (13) and cyclic trimer (17) derivatives of QZ59S-SSS were found to be the most and equally potent inhibitors of human P-gp (IC50=1.5 M). As the cyclic trimer and linear trimer compounds are equipotent, future studies should focus on noncyclic counterparts of cyclic peptides maintaining linear trimer length. A binding model of the linear trimer 13 within the drug binding site on the homology model of human P-gp represents an opportunity for future optimization, specifically replacing valine and thiazole groups in the noncyclic form. C1 [Singh, Satyakam; Patel, Bhargav A.; Talele, Tanaji T.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Queens, NY 11439 USA. [Prasad, Nagarajan Rajendra; Kapoor, Khyati; Chufan, Eduardo E.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@mail.nih.gov; talelet@stjohns.edu OI Singh, Satyakam/0000-0001-9115-3296 FU Department of Pharmaceutical Sciences of St. John's University; St. John's University [579-1110]; NIH, National Cancer Institute, Center for Cancer Research; Indian Council of Medical Research, New Delhi [Indo/FRC/452(Y-19)/2012-13IHD] FX This research was supported by the Department of Pharmaceutical Sciences of St. John's University and St. John's University Seed Grant No. 579-1110 (to T.T.T.). N.R.P., K.K., E.E.C., and S.V.A. were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Financial support from the Indian Council of Medical Research, New Delhi in the form of an International Fellowship for Young Indian Biomedical Scientists to N.R.P. is gratefully acknowledged (Indo/FRC/452(Y-19)/2012-13IHD). S.S. and T.T.T. are thankful to Dr. Sanjai Kumar and Dibyendu Dana for assisting in preparative HPLC, ESI-MS, and chiral HPLC analyses. NR 45 TC 3 Z9 3 U1 1 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4227 EI 1439-7633 J9 CHEMBIOCHEM JI ChemBioChem PD JAN 3 PY 2014 VL 15 IS 1 BP 157 EP 169 DI 10.1002/cbic.201300565 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 275MT UT WOS:000328682000019 PM 24288265 ER PT J AU Tuz, K Bachmann-Gagescu, R O'Day, DR Hua, K Isabella, CR Phelps, IG Stolarski, AE O'Roak, BJ Dempsey, JC Lourenco, C Alswaid, A Bonnemann, CG Medne, L Nampoothiri, S Stark, Z Leventer, RJ Topcu, M Cansu, A Jagadeesh, S Done, S Ishak, GE Glass, IA Shendure, J Neuhauss, SCF Haldeman-Englert, CR Doherty, D Ferland, RJ AF Tuz, Karma Bachmann-Gagescu, Ruxandra O'Day, Diana R. Hua, Kiet Isabella, Christine R. Phelps, Ian G. Stolarski, Allan E. O'Roak, Brian J. Dempsey, Jennifer C. Lourenco, Charles Alswaid, Abdulrahman Boennemann, Carsten G. Medne, Livija Nampoothiri, Sheela Stark, Zornitza Leventer, Richard J. Topcu, Meral Cansu, Ali Jagadeesh, Sujatha Done, Stephen Ishak, Gisele E. Glass, Ian A. Shendure, Jay Neuhauss, Stephan C. F. Haldeman-Englert, Chad R. Doherty, Dan Ferland, Russell J. TI Mutations in CSPP1 Cause Primary Cilia Abnormalities and Joubert Syndrome with or without Jeune Asphyxiating Thoracic Dystrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRANSITION ZONE; PROTEIN; LOCALIZATION; CILIOPATHIES; CILIOGENESIS; DISORDERS; SPECTRUM; DISEASE; GENES; MEMBRANE AB Joubert syndrome (JBTS) is a recessive ciliopathy in which a subset of affected individuals also have the skeletal dysplasia Jeune asphyxiating thoracic dystrophy (JATD). Here, we have identified biallelic truncating CSPP1 (centrosome and spindle pole associated protein 1) mutations in 19 JBTS-affected individuals, four of whom also have features of JATD. CSPP1 mutations explain similar to 5% of JBTS in our cohort, and despite truncating mutations in all affected individuals, the range of phenotypic severity is broad. Morpholino knockdown of cspp1 in zebrafish caused phenotypes reported in other zebrafish models of JBTS (curved body shape, pronephric cysts, and cerebellar abnormalities) and reduced ciliary localization of Arl13b, further supporting loss of CSPP1 function as a cause of JBTS. Fibroblasts from affected individuals with CSPP1 mutations showed reduced numbers of primary cilia and/or short primary cilia, as well as reduced axonemal localization of ciliary proteins ARL13B and adenylyl cyclase III. In summary, CSPP1 mutations are a major cause of the Joubert-Jeune phenotype in humans; however, the mechanism by which these mutations lead to both JBTS and JATD remains unknown. C1 [Tuz, Karma; Hua, Kiet; Stolarski, Allan E.; Ferland, Russell J.] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Bachmann-Gagescu, Ruxandra; Neuhauss, Stephan C. F.] Univ Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland. [Bachmann-Gagescu, Ruxandra] Univ Zurich, Inst Med Genet, CH-8603 Zurich, Switzerland. [O'Day, Diana R.; Isabella, Christine R.; Phelps, Ian G.; Dempsey, Jennifer C.; Glass, Ian A.; Doherty, Dan] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [O'Day, Diana R.; Isabella, Christine R.; Phelps, Ian G.; Dempsey, Jennifer C.; Glass, Ian A.; Doherty, Dan] Univ Washington, Dept Pediat, Div Dev Med, Seattle, WA 98195 USA. [O'Roak, Brian J.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Lourenco, Charles] Univ Sao Paulo, Sch Med Ribeirao Preto, Clin Hosp, Neurogenet Div, BR-14049900 Sao Paulo, Brazil. [Alswaid, Abdulrahman] King Abdul Aziz Med City, Dept Pediat, Riyadh 11426, Saudi Arabia. [Boennemann, Carsten G.] NIH, Neuromuscular & Neurogenet Disorders Childhood Se, John Edward Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Medne, Livija] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Nampoothiri, Sheela] AIMS Ponekkara PO, Amrita Inst Med Sci & Res Ctr, Dept Pediat Genet, Kochi 682041, Kerala, India. [Stark, Zornitza] Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Parkville, Vic 3052, Australia. [Leventer, Richard J.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Neurol, Parkville, Vic 3052, Australia. [Leventer, Richard J.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Pediat, Parkville, Vic 3052, Australia. [Leventer, Richard J.] Univ Melbourne, Parkville, Vic 3052, Australia. [Topcu, Meral] Hacettepe Univ, Fac Med, Ihsan Dogramaci Childrens Hosp, Dept Child Neurol, TR-06100 Ankara, Turkey. [Cansu, Ali] Karadeniz Tech Univ, Pediat Neurol Unit, TR-61080 Trabzon, Turkey. [Jagadeesh, Sujatha] MediScan Syst, Madras 600004, Tamil Nadu, India. [Done, Stephen; Ishak, Gisele E.] Univ Washington, Dept Radiol, Seattle, WA 98105 USA. [Done, Stephen; Ishak, Gisele E.] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Glass, Ian A.; Doherty, Dan] Seattle Childrens Hosp, Res Inst, Ctr Integrat Brain Res, Seattle, WA 98105 USA. [Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Haldeman-Englert, Chad R.] Wake Forest Sch Med, Dept Pediat, Med Genet Sect, Winston Salem, NC 27157 USA. [Ferland, Russell J.] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA. RP Doherty, D (reprint author), Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. EM ddoher@uw.edu; ferlanr@mail.amc.edu RI Bachmann-Gagescu, Ruxandra/A-8444-2016; OI Bachmann-Gagescu, Ruxandra/0000-0002-3571-5271; Ferland, Russell/0000-0002-8044-2479; Neuhauss, Stephan/0000-0002-9615-480X; O'Roak, Brian/0000-0002-4141-0095; Shendure, Jay/0000-0002-1516-1865 FU Swiss National Science Foundation [PZ00P3_142404]; March of Dimes Foundation [5-FY09-29]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS064077]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health (University of Washington Intellectual and Developmental Disabilities Research Center Genetics Core) [P30HD002274, R01NS064283] FX Our deepest thanks go to all of the individuals with Joubert syndrome and their families. This work was supported in part by the Swiss National Science Foundation (PZ00P3_142404 to R.B.-G.), the March of Dimes Foundation (5-FY09-29 to R.J.F.), and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01NS064077 and University of Washington Intellectual and Developmental Disabilities Research Center Genetics Core P30HD002274 to D.D. and R01NS064283 to R.J.F.). We also acknowledge private donations from the families of children with Joubert syndrome. NR 34 TC 28 Z9 29 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN 2 PY 2014 VL 94 IS 1 BP 62 EP 72 DI 10.1016/j.ajhg.2013.11.019 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 292FU UT WOS:000329888400006 PM 24360808 ER PT J AU Rehman, AU Santos-Cortez, RLP Morell, RJ Drummond, MC Ito, T Lee, K Khan, AA Basra, MAR Wasif, N Ayub, M Ali, RA Raza, SI Nickerson, DA Shendure, J Bamshad, M Riazuddin, S Billington, N Khan, SN Friedman, PL Griffith, AJ Ahmad, W Riazuddin, S Leal, SM Friedman, TB AF Rehman, Atteeq U. Santos-Cortez, Regie Lyn P. Morell, Robert J. Drummond, Meghan C. Ito, Taku Lee, Kwanghyuk Khan, Asma A. Basra, Muhammad Asim R. Wasif, Naveed Ayub, Muhammad Ali, Rana A. Raza, Syed I. Nickerson, Deborah A. Shendure, Jay Bamshad, Michael Riazuddin, Saima Billington, Neil Khan, Shaheen N. Friedman, Penelope L. Griffith, Andrew J. Ahmad, Wasim Riazuddin, Sheikh Leal, Suzanne M. Friedman, Thomas B. CA Univ Washington TI Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUDITORY NEUROPATHY; HAIR-CELLS; MET RECEPTOR; PROTEIN; HUMANS; MECHANOTRANSDUCTION; FAMILY; ACTIN; GAPS; RAB AB Inherited deafness is clinically and genetically heterogeneous. We recently mapped DFNB86, a locus associated with nonsyndromic deafness, to chromosome 16p. In this study, whole-exome sequencing was performed with genomic DNA from affected individuals from three large consanguineous families in which markers linked to DFNB86 segregate with profound deafness. Analyses of these data revealed homozygous mutation c.208G>T (p.Asp70Tyr) or c.878G>C (p.Arg293Pro) in TBC1D24 as the underlying cause of deafness in the three families. Sanger sequence analysis of TBC1D24 in an additional large family in which deafness segregates with DFNB86 identified the c.208G>T (p.Asp70Tyr) substitution. These mutations affect TBC1D24 amino acid residues that are conserved in orthologs ranging from fruit fly to human. Neither variant was observed in databases of single-nucleotide variants or in 634 chromosomes from ethnically matched control subjects. TBC1D24 in the mouse inner ear was immunolocalized predominantly to spiral ganglion neurons, indicating that DFNB86 deafness might be an auditory neuropathy spectrum disorder. Previously, six recessive mutations in TBC1D24 were reported to cause seizures (hearing loss was not reported) ranging in severity from epilepsy with otherwise normal development to epileptic encephalopathy resulting in childhood death. Two of our four families in which deafness segregates with mutant alleles of TBC1D24 were available for neurological examination. Cosegregation of epilepsy and deafness was not observed in these two families. Although the causal relationship between genotype and phenotype is not presently understood, our findings, combined with published data, indicate that recessive alleles of TBC1D24 can cause either epilepsy or nonsyndromic deafness. C1 [Rehman, Atteeq U.; Morell, Robert J.; Drummond, Meghan C.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. [Santos-Cortez, Regie Lyn P.; Lee, Kwanghyuk; Leal, Suzanne M.] Baylor Coll Med, Ctr Stat Genet, Dept Mol & Human Genet, Houston, TX 77030 USA. [Ito, Taku; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA. [Khan, Asma A.; Basra, Muhammad Asim R.; Ali, Rana A.; Khan, Shaheen N.; Riazuddin, Sheikh] Univ Punjab, Ctr Excellence Mol Biol, Lahore 54500, Pakistan. [Wasif, Naveed] Univ Lahore, Inst Mol Biol & Biotechnol, Ctr Res Mol Med, Lahore 54000, Pakistan. [Ayub, Muhammad] Univ Baluchistan, Inst Biochem, Quetta 87300, Pakistan. [Raza, Syed I.; Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad 45320, Pakistan. [Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Riazuddin, Saima] Cincinnati Childrens Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA. [Riazuddin, Saima] Univ Cincinnati, Coll Med, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH 45267 USA. [Billington, Neil] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Friedman, Penelope L.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore 54550, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Jinnah Hosp Complex, Lahore 54550, Pakistan. RP Leal, SM (reprint author), Baylor Coll Med, Ctr Stat Genet, Dept Mol & Human Genet, Houston, TX 77030 USA. EM sleal@bcm.edu; friedman@nidcd.nih.gov RI Wasif, Naveed/J-1807-2015; OI Morell, Robert/0000-0003-1537-7356; Shendure, Jay/0000-0002-1516-1865 FU National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders (NIDCD) [R01 DC011651, R01 DC003594]; Higher Education Commission; Ministry of Science and Technology of Pakistan; International Center for Genetic Engineering and Biotechnology in Trieste [CRP/PAK08-01, 08/009]; NIH National Human Genome Research Institute; National Heart, Lung, and Blood Institute (NHLBI) [U54 HG006493]; NIH [N01 HG65403]; NHLBI [HL004232]; [DC000060-12]; [DC000039-16] FX We thank the subjects who participated in this study, as well as Dennis Drayna, Katie S. Kindt, and Julie Schultz for their critiques of our manuscript. We also thank Barbara Zwiesler, Elizabeth Wilson, Roger Murayi, and Hashim Raza for technical assistance. This study was supported by National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders (NIDCD) grants R01 DC011651 and R01 DC003594 to S.M.L., the Higher Education Commission, the Ministry of Science and Technology of Pakistan (Sh.R. and W.A.), the International Center for Genetic Engineering and Biotechnology in Trieste (CRP/PAK08-01 contract 08/009 to Sh.R.), and the NIH National Human Genome Research Institute and National Heart, Lung, and Blood Institute (NHLBI) (U54 HG006493 to the University of Washington Center for Mendelian Genomics). Genotyping for S.M.L. was performed at the Center for Inherited Disease Research, which is funded by the NIH (contract number N01 HG65403 to Johns Hopkins University). N.B. was supported by NHLBI intramural funds HL004232 to James Sellers. Work at the NIH NIDCD was supported by intramural funds DC000060-12 to A.J.G. and DC000039-16 to T.B.F. NR 37 TC 25 Z9 32 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN 2 PY 2014 VL 94 IS 1 BP 144 EP 152 DI 10.1016/j.ajhg.2013.12.004 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 292FU UT WOS:000329888400016 PM 24387994 ER PT J AU Rezvani, K Barrett, J AF Rezvani, Katayoun Barrett, John TI STAT3: the "Achilles" heel for AML? SO BLOOD LA English DT Editorial Material ID SIGNAL TRANSDUCER; ACTIVATOR; IMMUNITY; THERAPY C1 [Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Barrett, John] NIH, Bethesda, MD USA. RP Rezvani, K (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 9 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 2 PY 2014 VL 123 IS 1 BP 1 EP 2 DI 10.1182/blood-2013-11-537092 PG 2 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300001 PM 24385491 ER PT J AU Speak, AO Vruchte, DT Davis, LC Morgan, AJ Smith, DA Yanjanin, NM Simmons, L Hartung, R Runz, H Mengel, E Beck, M Imrie, J Jacklin, E Wraith, JE Hendriksz, C Lachmann, R Cognet, C Sidhu, R Fujiwara, H Ory, DS Galione, A Porter, FD Vivier, E Platt, FM AF Speak, Anneliese O. Vruchte, Danielle te Davis, Lianne C. Morgan, Anthony J. Smith, David A. Yanjanin, Nicole M. Simmons, Louise Hartung, Ralf Runz, Heiko Mengel, Eugen Beck, Michael Imrie, Jackie Jacklin, Elizabeth Wraith, James E. Hendriksz, Christian Lachmann, Robin Cognet, Celine Sidhu, Rohini Fujiwara, Hideji Ory, Daniel S. Galione, Antony Porter, Forbes D. Vivier, Eric Platt, Frances M. TI Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1 SO BLOOD LA English DT Article ID MOUSE NK CELLS; CHRONIC NEURODEGENERATION; CHOLESTEROL HOMEOSTASIS; TRANSPORTER SPNS2; STORAGE DISEASE; CALCIUM INFLUX; SPHINGOSINE-1-PHOSPHATE; INFLAMMATION; MATURATION; TRAFFICKING AB Niemann-Pick type C (NPC) is a neurodegenerative lysosomal storage disorder caused by defects in the lysosomal proteins NPC1 or NPC2. NPC cells are characterized by reduced lysosomal calcium levels and impaired sphingosine transport from lysosomes. Natural killer (NK) cells kill virally infected/transformed cells via degranulation of lysosome-related organelles. Their trafficking from lymphoid tissues into the circulation is dependent on sphingosine-1-phosphate (S1P) gradients, sensed by S1P receptor 5 (S1P(5)). We hypothesized that NK-cell function and trafficking could be affected in NPC disease due to the combined effects of the lysosomal calcium defect and sphingosine storage. In an NPC1 mouse model, we found the frequency of NK cells was altered and phenocopied S1P(5)-deficient mice, consistent with defects in S1P levels. NK cells from NPC1 mice also had a defect in cytotoxicity due to a failure in degranulation of cytotoxic granules, which was associated with reduced lysosomal calcium levels. Affected NPC1 patients and NPC1 heterozygote carriers had reduced NK-cell numbers in their blood and showed similar phenotypic and developmental changes to those observed in the NPC1 mouse. These findings highlight the effects of lysosomal storage on the peripheral immune system. C1 [Speak, Anneliese O.; Vruchte, Danielle te; Davis, Lianne C.; Morgan, Anthony J.; Smith, David A.; Galione, Antony; Platt, Frances M.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. [Yanjanin, Nicole M.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, US Dept HHS, Bethesda, MD USA. [Simmons, Louise; Hendriksz, Christian] Birmingham Childrens Hosp NHS Fdn Trust, Birmingham, W Midlands, England. [Hartung, Ralf; Runz, Heiko; Mengel, Eugen; Beck, Michael] Johannes Gutenberg Univ Mainz, Childrens Hosp, Univ Med Ctr, Mainz, Germany. [Imrie, Jackie; Jacklin, Elizabeth; Wraith, James E.] Royal Manchester Childrens Hosp, Willink Biochem Genet Unit, Manchester M27 1HA, Lancs, England. [Lachmann, Robin] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Cognet, Celine; Vivier, Eric] Hop Conception, Assistance Publ Hop Marseille, Marseille, France. [Cognet, Celine; Vivier, Eric] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France. [Sidhu, Rohini; Fujiwara, Hideji; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO USA. RP Platt, FM (reprint author), Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England. EM frances.platt@pharm.ox.ac.uk RI Sidhu, Rohini/G-3547-2012; OI Speak, Anneliese/0000-0003-4890-4685 FU MRC [GO700851]; Action Medical Research; SOAR-NPC; Wellcome Trust [084102/Z/07/Z, 084631]; Royal Society; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Office of Rare Diseases; National Insitutes of Health Clinical Centre; APMRF; DART; Washington University Metabolomics Facility FX A.O.S. is funded by the MRC (GO700851), D.t.V. by Action Medical Research, D.A.S. by SOAR-NPC, and L.C.D. and A.J.M. by the Wellcome Trust (084102/Z/07/Z). An equipment grant from the Wellcome Trust funded the flow cytometer (084631). F.M.P. is a Royal Society Wolfson Research Merit Award holder. This work was supported in part by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and a Bench to Bedside grant from the Office of Rare Diseases and the National Insitutes of Health Clinical Centre (F.D.P.). N.M.Y. was supported by APMRF and DART. This work was supported by a grant from DART (D.S.O.) and the Washington University Metabolomics Facility. NR 49 TC 8 Z9 8 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 2 PY 2014 VL 123 IS 1 BP 51 EP 60 DI 10.1182/blood-2013-03-488692 PG 10 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300014 PM 24235134 ER PT J AU Ciappio, ED Krausz, KW Rochman, M Furusawa, T Bonzo, JA Tessarollo, L Gonzalez, FJ Bustin, M AF Ciappio, Eric D. Krausz, Kristopher W. Rochman, Mark Furusawa, Takashi Bonzo, Jessica A. Tessarollo, Lino Gonzalez, Frank J. Bustin, Michael TI Metabolomics Reveals a Role for the Chromatin-Binding Protein HMGN5 in Glutathione Metabolism SO PLOS ONE LA English DT Article ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; HISTONE H1; EXPRESSION; TRANSCRIPTION; DATABASE; PROFILE; FAMILY; METLIN AB High mobility group nucleosome-binding protein 5 (HMGN5) is a chromatin architectural protein that binds specifically to nucleosomes and reduces the compaction of the chromatin fiber. The protein is present in most vertebrate tissues however the physiological function of this protein is unknown. To examine the function of HMGN5 in vivo, mice lacking the nucleosome-binding domain of HMGN5 were generated and characterized. Serological analysis revealed that compared to wild-type littermates (Hmgn5(+/Y)), mice with a targeted mutation in the HMGN5 gene (Hmgn5(tm1/Y)), had elevated serum albumin, non-HDL cholesterol, triglycerides, and alanine transaminase, suggesting mild hepatic abnormalities. Metabolomics analysis of liver extracts and urine revealed clear differences in metabolites between Hmgn5(tm1/Y) and their Hmgn5(+/Y) littermates. Hmgn5(tm1/Y) mice had a significant increase in hepatic glutathione levels and decreased urinary concentrations of betaine, phenylacetylglycine, and creatine, all of which are metabolically related to the glutathione precursor glycine. Microarray and qPCR analysis revealed that expression of two genes affecting glutathione metabolism, glutathione peroxidase 6 (Gpx6) and hexokinase 1 (Hk1), was significantly decreased in Hmgn5(tm1/Y) mouse liver tissue. Analysis of chromatin structure by DNase I digestion revealed alterations in the chromatin structure of these genes in the livers of Hmgn5(tm1/Y) mice. Thus, functional loss of HMGN5 leads to changes in transcription of Gpx6 and Hk1 that alter glutathione metabolism. C1 [Ciappio, Eric D.; Krausz, Kristopher W.; Rochman, Mark; Furusawa, Takashi; Bonzo, Jessica A.; Gonzalez, Frank J.; Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Bustin, M (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Center for Cancer Research, intramural program of the National Cancer Institute, National Institutes of Health; United States-Israeli Binational foundation [2009326] FX This was funded by the Center for Cancer Research, intramural program of the National Cancer Institute, National Institutes of Health, and by grant #2009326 from the United States-Israeli Binational foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 6 Z9 6 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 2 PY 2014 VL 9 IS 1 AR e84583 DI 10.1371/journal.pone.0084583 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286ID UT WOS:000329460100067 PM 24392144 ER PT J AU Dolinska, MB Kovaleva, E Backlund, P Wingfield, PT Brooks, BP Sergeev, YV AF Dolinska, Monika B. Kovaleva, Elena Backlund, Peter Wingfield, Paul T. Brooks, Brian P. Sergeev, Yuri V. TI Albinism-Causing Mutations in Recombinant Human Tyrosinase Alter Intrinsic Enzymatic Activity SO PLOS ONE LA English DT Article ID I OCULOCUTANEOUS ALBINISM; MELANOMA-CELLS; MOLECULAR-BASIS; METABOLIC INFORMATION; ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; MELANOSOMAL PH; TYPE-1 OCA1; PROTEINS; GENE AB Background: Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. Methodology/Principal Findings: The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of > 1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37 degrees C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. Conclusions/Significance: The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1. C1 [Dolinska, Monika B.; Brooks, Brian P.; Sergeev, Yuri V.] NEI, NIH, Bethesda, MD 20892 USA. [Kovaleva, Elena] Chesapeake PERL, Savage, MD USA. [Backlund, Peter] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Wingfield, Paul T.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Brooks, BP (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM brooksb@nei.nih.gov; sergeevy@nei.nih.gov FU Intramural program of National Eye Institute, National Institutes of Health [Z01-EY000476-01] FX This work was supported by the Intramural program of National Eye Institute, National Institutes of Health (Z01-EY000476-01 to YVS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 6 Z9 6 U1 4 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 2 PY 2014 VL 9 IS 1 AR e84494 DI 10.1371/journal.pone.0084494 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286ID UT WOS:000329460100064 PM 24392141 ER PT J AU Troxell, B Zhang, JJ Bourret, TJ Zeng, MY Blum, J Gherardini, F Hassan, HM Yang, XF AF Troxell, Bryan Zhang, Jun-Jie Bourret, Travis J. Zeng, Melody Yue Blum, Janice Gherardini, Frank Hassan, Hosni M. Yang, X. Frank TI Pyruvate Protects Pathogenic Spirochetes from H2O2 Killing SO PLOS ONE LA English DT Article ID LYME-DISEASE AGENT; A DISULFIDE REDUCTASE; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; BORRELIA-BURGDORFERI; HYDROGEN-PEROXIDE; LEPTOSPIRA-INTERROGANS; ANAEROBIC METABOLISM; HUMAN-NEUTROPHILS; MAMMALIAN HOST AB Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (approximate to 0.6 mu M per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected Delta uvrB and Delta mutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection. C1 [Troxell, Bryan; Zhang, Jun-Jie; Zeng, Melody Yue; Blum, Janice; Yang, X. Frank] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Bourret, Travis J.] Univ Nebraska Kearney, Dept Biol, Kearney, NE USA. [Hassan, Hosni M.] N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. [Gherardini, Frank] NIAID, Lab Zoonot Pathogens, NIH, Hamilton, MT USA. RP Hassan, HM (reprint author), N Carolina State Univ, Prestage Dept Poultry Sci, Raleigh, NC 27695 USA. EM hmhassan@ncsu.edu; xfyang@iupui.edu RI zhang, junjie/P-2376-2015; OI zhang, junjie/0000-0002-5108-2072; Troxell, Bryan/0000-0002-0533-6721; Bourret, Travis/0000-0002-4154-929X FU NIH [R01 AI083640]; Lilly Endowment, Inc.; National Center for Research Resources [5P20RR016469]; National Institute for General Medical Science (NIGMS) [5P20GM103427] FX Funding for this work was partially provided by NIH grant R01 AI083640, Indiana INGEN and METACyt grants of Indiana University, funded by the Lilly Endowment, Inc. (to XFY), National Center for Research Resources (5P20RR016469) and the National Institute for General Medical Science (NIGMS) (5P20GM103427) (to TJB). A component of the National Institutes of Health (NIH) and its contents are the sole responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. BT and MYZ were supported by NIH T32 training grant 5T32AI060519. This investigation was partially conducted in a facility constructed with support from research facilities improvement program grant number C06 RR015481-01 from National Center for Research Resources, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 8 Z9 8 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 2 PY 2014 VL 9 IS 1 AR e84625 DI 10.1371/journal.pone.0084625 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286ID UT WOS:000329460100070 PM 24392147 ER PT J AU Hao, M Wang, YL Bryant, SH AF Hao, Ming Wang, Yanli Bryant, Stephen H. TI An efficient algorithm coupled with synthetic minority over-sampling technique to classify imbalanced PubChem BioAssay data SO ANALYTICA CHIMICA ACTA LA English DT Article DE High throughput screening; Under-sampling; Over-sampling; PubChem; Imbalanced classification ID THROUGHPUT SCREENING DATA; SUPPORT VECTOR MACHINES; RANDOM FOREST; DATA SETS; SMALL MOLECULES; CLASSIFICATION; PREDICTION; MODELS; DESCRIPTORS; REGRESSION AB It is common that imbalanced datasets are often generated from high-throughput screening (HTS). For a given dataset without taking into account the imbalanced nature, most classification methods tend to produce high predictive accuracy for the majority class, but significantly poor performance for the minority class. In this work, an efficient algorithm, GLMBoost, coupled with Synthetic Minority Over-sampling TEchnique (SMOTE) is developed and utilized to overcome the problem for several imbalanced datasets from PubChem BioAssay. By applying the proposed combinatorial method, those data of rare samples (active compounds), for which usually poor results are generated, can be detected apparently with high balanced accuracy (Gmean). As a comparison with GLMBoost, Random Forest (RF) combined with SMOTE is also adopted to classify the same datasets. Our results show that the former (GLMBoost + SMOTE) not only exhibits higher performance as measured by the percentage of correct classification for the rare samples (Sensitivity) and Gmean, but also demonstrates greater computational efficiency than the latter (RF + SMOTE). Therefore, we hope that the proposed combinatorial algorithm based on GLMBoost and SMOTE could be extensively used to tackle the imbalanced classification problem. Published by Elsevier B.V. C1 [Hao, Ming; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX This research is supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 55 TC 13 Z9 13 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 EI 1873-4324 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JAN 2 PY 2014 VL 806 BP 117 EP 127 DI 10.1016/j.aca.2013.10.050 PG 11 WC Chemistry, Analytical SC Chemistry GA 273XF UT WOS:000328568900011 PM 24331047 ER PT J AU Chen, KG Mallon, BS McKay, RDG Robey, PG AF Chen, Kevin G. Mallon, Barbara S. McKay, Ronald D. G. Robey, Pamela G. TI Human Pluripotent Stem Cell Culture: Considerations for Maintenance, Expansion, and Therapeutics SO CELL STEM CELL LA English DT Review ID HUMAN EMBRYONIC STEM; TERM SELF-RENEWAL; HUMAN ES CELLS; SUSPENSION-CULTURE; DEFINED CONDITIONS; MICROCARRIER CULTURES; CLINICAL-APPLICATION; SYNTHETIC SURFACES; IN-VIVO; DIFFERENTIATION AB Human pluripotent stem cells (hPSCs) provide powerful resources for application in regenerative medicine and pharmaceutical development. In the past decade, various methods have been developed for large-scale hPSC culture that rely on combined use of multiple growth components, including media containing various growth factors, extracellular matrices, 3D environmental cues, and modes of multicellular association. In this Protocol Review, we dissect these growth components by comparing cell culture methods and identifying the benefits and pitfalls associated with each one. We further provide criteria, considerations, and suggestions to achieve optimal cell growth for hPSC expansion, differentiation, and use in future therapeutic applications. C1 [Chen, Kevin G.; Mallon, Barbara S.] Natl Inst Neurol Disorders & Stroke, NIH Stem Cell Unit, NIH, Bethesda, MD 20892 USA. [McKay, Ronald D. G.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chen, KG (reprint author), Natl Inst Neurol Disorders & Stroke, NIH Stem Cell Unit, NIH, Bethesda, MD 20892 USA. EM cheng@mail.nih.gov RI Robey, Pamela/H-1429-2011; Chen, Kevin/D-6769-2011 OI Robey, Pamela/0000-0002-5316-5576; Chen, Kevin/0000-0003-2983-6330 FU Intramural Research Program of the National Institutes of Health (NIH) at the National Institute of Neurological Disorders and Stroke FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH) at the National Institute of Neurological Disorders and Stroke. We thank Dr. Peter Zandstra, Dr. Kyeyoon Park, Dr. Daniel Hoeppner, and Ms. Rebecca Hamilton for discussion and suggestions. We thank Mr. George Leiman for editorial assistance. NR 104 TC 53 Z9 53 U1 12 U2 59 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JAN 2 PY 2014 VL 14 IS 1 BP 13 EP 26 DI 10.1016/j.stem.2013.12.005 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287WB UT WOS:000329571900006 PM 24388173 ER PT J AU Philbin, MM Tanner, AE DuVal, A Ellen, J Kapogiannis, B Fortenberry, JD AF Philbin, Morgan M. Tanner, Amanda E. DuVal, Anna Ellen, Jonathan Kapogiannis, Bill Fortenberry, J. Dennis TI Linking HIV-positive adolescents to care in 15 different clinics across the United States: Creating solutions to address structural barriers for linkage to care SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE adolescents; HIV; AIDS; linkage to care; structural barriers; qualitative methods ID ANTIRETROVIRAL TREATMENT ACCESS; HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICAL-CARE; HEALTH-CARE; CHRONIC ILLNESS; INFECTED WOMEN; PUBLIC-HEALTH; RETENTION; THERAPY; INTERVENTIONS AB Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents' readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering uninsured patients with clinic funds is imperative to achieving the goal of increasing linkage to care rates for newly diagnosed adolescents. C1 [Philbin, Morgan M.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Tanner, Amanda E.] Univ N Carolina, Dept Publ Hlth Educ, Greensboro, NC 27412 USA. [DuVal, Anna; Ellen, Jonathan] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Kapogiannis, Bill] NIH, US Dept HHS, Bethesda, MD 20892 USA. [Fortenberry, J. Dennis] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. RP Philbin, MM (reprint author), Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. EM mphilbin@jhsph.edu FU NICHD NIH HHS [U01 HD040474, U01 HD040533]; NIMH NIH HHS [P30 MH043520, T32 MH019139] NR 42 TC 20 Z9 20 U1 3 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2014 VL 26 IS 1 BP 12 EP 19 DI 10.1080/09540121.2013.808730 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 276DK UT WOS:000328728100002 PM 23777542 ER PT J AU Usitalo, A Leister, E Tassiopoulos, K Allison, S Malee, K Paul, ME Smith, R Van Dyke, RB Seage, GR Mellins, CA AF Usitalo, Ann Leister, Erin Tassiopoulos, Katherine Allison, Susannah Malee, Kathleen Paul, Mary E. Smith, Renee Van Dyke, Russell B. Seage, George R., III Mellins, Claude A. TI Relationship between viral load and self-report measures of medication adherence among youth with perinatal HIV infection SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; adherence; antiretroviral; pediatric ID ACTIVE ANTIRETROVIRAL THERAPY; OPTIMAL RECALL PERIOD; CLINICAL MANAGEMENT; CHILDREN; RECOMMENDATIONS; ADOLESCENTS; ASSOCIATION; PREDICTORS; RESISTANCE; CAREGIVER AB Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV +), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold-standard assessment in HIV research, they are costly, can overestimate nonadherence and are not practical for routine care. Thus, the development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+youth aged 7-16 (n = 289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/400 copies/mL. Lower adherence was significantly associated with VL >400 copies/mL across most indicators, including 1 missed dose in past seven days [youth report: OR = 2.78 (95% CI, 1.46-5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age 13 years and living with biological mother or relative were associated with VL >400 copies/mL. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence. C1 [Usitalo, Ann] Univ Florida, Div Pediat Infect Dis & Immunol, Dept Pediat, Jacksonville, FL 32209 USA. [Leister, Erin] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Tassiopoulos, Katherine; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Allison, Susannah] NIMH, Infant Res Program, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Allison, Susannah] NIMH, Child Res Program, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Allison, Susannah] NIMH, Adolescent Res Program, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Malee, Kathleen] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Paul, Mary E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Smith, Renee] Univ Illinois, Dept Pediat, Chicago, IL USA. [Van Dyke, Russell B.] Tulane Univ, Sch Med, Dept Pediat, Infect Dis Sect, New Orleans, LA 70112 USA. [Mellins, Claude A.] Columbia Univ, HIV Ctr Clin & Behav Studies, New York, NY USA. RP Usitalo, A (reprint author), Univ Florida, Div Pediat Infect Dis & Immunol, Dept Pediat, Jacksonville, FL 32209 USA. EM ann.usitalo@jax.ufl.edu FU NCATS NIH HHS [UL1 TR001082]; NICHD NIH HHS [U01 HD052104, U01 HD 052104-01, U01 HD052102, U01 HD0522102-04]; NIMH NIH HHS [P30 MH043520] NR 34 TC 16 Z9 16 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2014 VL 26 IS 1 BP 107 EP 115 DI 10.1080/09540121.2013.802280 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 276DK UT WOS:000328728100014 PM 23800360 ER PT J AU Cui, YH Jin, Z Chen, X He, Y Liang, X Zheng, Y AF Cui, Yonghua Jin, Zhen Chen, Xu He, Yong Liang, Xia Zheng, Yi TI Abnormal baseline brain activity in drug-naive patients with Tourette syndrome: a resting-state fMRI study SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE Tourette syndrome; resting-state fMRI; amplitude of low-frequency fluctuation; fractional amplitude of low-frequency fluctuation; cortico-striatal-thalamo-cortical ID OBSESSIVE-COMPULSIVE DISORDER; FUNCTIONAL CONNECTIVITY MRI; TIC SEVERITY; DEFAULT MODE; EXECUTIVE FUNCTION; STRUCTURAL-CHANGES; PREFRONTAL CORTEX; GANGLIA VOLUMES; CHILDREN; CIRCUITS AB Tourette syndrome (TS) is a childhood-onset chronic disorder characterized by the presence of multiple motor and vocal tics. This study investigated spontaneous low-frequency fluctuations in TS patients during resting-state functional magnetic resonance imaging (rs-fMRI) scans. We obtained rs-fMRI scans from 17 drug-naive TS children and 15 demographically matched healthy children. We computed the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) of rs-fMRI data to measure spontaneous brain activity, and assessed the between-group differences in ALFF/fALFF and the relationship between ALFF/fALFF and tic severity scores. Our results showed that the children with TS exhibited significantly decreased ALFF in the posterior cingulate gyrus/precuneus and bilateral parietal gyrus. fALFF was decreased in TS children in the anterior cingulated cortex, bilateral middle and superior frontal cortices and superior parietal lobule, and increased in the left putamen and bilateral thalamus. Moreover, we found significantly positive correlations between fALFF and tic severity scores in the right thalamus. Our study provides empirical evidence for abnormal spontaneous neuronal activity in TS patients, which may implicate the underlying neurophysiological mechanism in TS and demonstrate the possibility of applying ALFF/fALFF for clinical TS studies. C1 [Cui, Yonghua; Chen, Xu; Zheng, Yi] Capital Med Univ, Dept Pediat, Beijing An Ding Hosp, Beijing 100088, Peoples R China. [Jin, Zhen] Peoples Liberat Army, Hosp 306, Dept Med Imaging, Beijing, Peoples R China. [He, Yong; Liang, Xia] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [He, Yong; Liang, Xia] Beijing Normal Univ, Int Digital Grp, McGovern Inst Brain Res, Beijing 100875, Peoples R China. [He, Yong] Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China. [Liang, Xia] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RP Zheng, Y (reprint author), Capital Med Univ, Dept Pediat, Beijing An Ding Hosp, Beijing 100088, Peoples R China. EM xia.liang@nih.gov; yizheng@ccmu.edu.cn FU Natural Science Foundation of China (NSFC) [81071108]; Natural Science Foundation of Beijing City (NSFB) [7082045]; Capital Medical Developmental Foundation [20093138] FX This work was supported by a Natural Science Foundation of China (NSFC) award to Yi Zheng (81071108), Natural Science Foundation of Beijing City (NSFB) award to Yi Zheng (7082045) and Capital Medical Developmental Foundation award to Yonghua Cui (20093138). NR 56 TC 6 Z9 6 U1 3 U2 11 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JAN 2 PY 2014 VL 7 AR 913 DI 10.3389/fnhum.2013.00913 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 284YG UT WOS:000329357700001 PM 24427134 ER PT J AU Cooper, CJ Murphy, TP Cutlip, DE Jamerson, K Henrich, W Reid, DM Cohen, DJ Matsumoto, AH Steffes, M Jaff, MR Prince, MR Lewis, EF Tuttle, KR Shapiro, JI Rundback, JH Massaro, JM D'Agostino, RB Dworkin, LD AF Cooper, Christopher J. Murphy, Timothy P. Cutlip, Donald E. Jamerson, Kenneth Henrich, William Reid, Diane M. Cohen, David J. Matsumoto, Alan H. Steffes, Michael Jaff, Michael R. Prince, Martin R. Lewis, Eldrin F. Tuttle, Katherine R. Shapiro, Joseph I. Rundback, John H. Massaro, Joseph M. D'Agostino, Ralph B. Dworkin, Lance D. CA Coral Investigators TI Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNSUCCESSFUL BALLOON ANGIOPLASTY; SYSTOLIC BLOOD-PRESSURE; RENOVASCULAR DISEASE; RANDOMIZED-TRIAL; HYPERTENSION; REVASCULARIZATION; PREVALENCE; PREVENTION; PLACEMENT AB BackgroundAtherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. MethodsWe randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). ResultsOver a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). ConclusionsRenal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.) C1 [Cooper, Christopher J.] Univ Toledo, Dept Med, Toledo, OH 43614 USA. [Murphy, Timothy P.; Dworkin, Lance D.] Rhode Isl Hosp, Providence, RI USA. [Murphy, Timothy P.; Dworkin, Lance D.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Cutlip, Donald E.; Massaro, Joseph M.; D'Agostino, Ralph B.] Harvard Clin Res Inst, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lewis, Eldrin F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Agostino, Ralph B.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Jamerson, Kenneth] Univ Michigan, Ann Arbor, MI 48109 USA. [Henrich, William] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Reid, Diane M.] NHLBI, Bethesda, MD 20892 USA. [Cohen, David J.] Univ Missouri, Kansas City Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, KS USA. [Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA. [Steffes, Michael] Univ Minnesota, Minneapolis, MN USA. [Prince, Martin R.] Weill Cornell Med Ctr, New York, NY USA. [Tuttle, Katherine R.] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Tuttle, Katherine R.] Univ Washington, Sch Med, Spokane, WA USA. [Shapiro, Joseph I.] Marshall Univ, Huntington, WV USA. [Rundback, John H.] Holy Name Med Ctr, Teaneck, NJ USA. RP Cooper, CJ (reprint author), Univ Toledo, Dept Med, 3000 Arlington Ave,MS 1036, Toledo, OH 43614 USA. EM christopher.cooper@utoledo.edu RI Prince, Martin/S-6850-2016; OI Mudge, David/0000-0002-4112-5550; Luft, Friedrich/0000-0002-8635-1199; Prince, Martin/0000-0002-9883-0584; Brilakis, Emmanouil/0000-0001-9416-9701 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [U01HL071556, U01HL072734, U01HL072735, U01HL072736, U01HL072737]; Abbott; AstraZeneca; Eli Lilly; Medtronic; Boston Scientific; Biomet; Janssen; Medicines Company; Novartis; Amgen; Sanofi Aventis; VIVA Physicians; Covidien; Biotronik; St. Jude; CSI FX Supported by grants (U01HL071556, U01HL072734, U01HL072735, U01HL072736, and U01HL072737) from the National Heart, Lung, and Blood Institute of the National Institutes of Health.; Dr. Murphy reports holding equity interest in Summa Therapeutics. Dr. Cutlip reports that his institution holds research contracts with Medtronic, Boston Scientific, and Abbott Vascular. Dr. Cohen reports receiving personal fees from Abbott, AstraZeneca, Eli Lilly, and Medtronic, and grant support from Abbott, AstraZeneca, Eli Lilly, Medtronic, Boston Scientific, Biomet, and Janssen. Dr. Matsumoto reports receiving consulting fees from Boston Scientific and the Medicines Company and grant support from Medtronic, Cook and W. L. Gore. Dr. Jaff reports receiving consulting fees from AstraZeneca and serving as an uncompensated advisor to Cordis, Boston Scientific, Abbott, Covidien, and Medtronic. Dr. Lewis reports receiving grant support from Novartis, Amgen, and Sanofi Aventis. Dr. Tuttle reports receiving consulting fees and grant support from Eli Lilly. Dr. Rundback reports receiving fees for board membership from VIVA Physicians, personal fees from Covidien, Biotronik, and St. Jude, and lecture fees from Covidien and CSI. No other potential conflict of interest relevant to this article was reported. NR 26 TC 229 Z9 241 U1 1 U2 29 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 13 EP 22 DI 10.1056/NEJMoa1310753 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100006 PM 24245566 ER PT J AU Acker, MA Parides, MK Perrault, LP Moskowitz, AJ Gelijns, AC Voisine, P Smith, PK Hung, JW Blackstone, EH Puskas, JD Argenziano, M Gammie, JS Mack, M Ascheim, DD Bagiella, E Moquete, EG Ferguson, TB Horvath, KA Geller, NL Miller, MA Woo, YJ D'Alessandro, DA Ailawadi, G Dagenais, F Gardner, TJ O'Gara, PT Michler, RE Kron, IL AF Acker, Michael A. Parides, Michael K. Perrault, Louis P. Moskowitz, Alan J. Gelijns, Annetine C. Voisine, Pierre Smith, Peter K. Hung, Judy W. Blackstone, Eugene H. Puskas, John D. Argenziano, Michael Gammie, James S. Mack, Michael Ascheim, Deborah D. Bagiella, Emilia Moquete, Ellen G. Ferguson, T. Bruce Horvath, Keith A. Geller, Nancy L. Miller, Marissa A. Woo, Y. Joseph D'Alessandro, David A. Ailawadi, Gorav Dagenais, Francois Gardner, Timothy J. O'Gara, Patrick T. Michler, Robert E. Kron, Irving L. TI Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LONG-TERM SURVIVAL; CARDIAC-RESYNCHRONIZATION THERAPY; END-SYSTOLIC VOLUME; HEART-FAILURE; MYOCARDIAL-INFARCTION; SURGICAL-MANAGEMENT; CLINICAL-TRIALS; DISEASE; IMPACT; CARDIOMYOPATHY AB BackgroundIschemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. MethodsWe randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. ResultsAt 12 months, the mean LVESVI among surviving patients was 54.625.0 ml per square meter of body-surface area in the repair group and 60.731.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. ConclusionsWe observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.) C1 [Acker, Michael A.; Woo, Y. Joseph] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Parides, Michael K.; Moskowitz, Alan J.; Gelijns, Annetine C.; Ascheim, Deborah D.; Bagiella, Emilia; Moquete, Ellen G.] Mt Sinai Sch Med, Int Ctr Hlth Outcomes & Innovat Res, Dept Hlth Evidence & Policy, New York, NY USA. [Argenziano, Michael] Columbia Univ, Coll Phys & Surg, Div Cardiothorac Surg, Dept Surg, New York, NY 10027 USA. [D'Alessandro, David A.; Michler, Robert E.] Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [D'Alessandro, David A.; Michler, Robert E.] Albert Einstein Coll Med, New York, NY USA. [Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Voisine, Pierre; Dagenais, Francois] Hop Laval, Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Smith, Peter K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Ferguson, T. Bruce] E Carolina Univ, E Carolina Heart Inst, Dept Cardiovasc Sci, Greenville, NC USA. [Hung, Judy W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Blackstone, Eugene H.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH USA. [Puskas, John D.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA. [Gammie, James S.] Univ Maryland, Sch Med, Div Cardiac Surg, Baltimore, MD 21201 USA. [Mack, Michael] Baylor Res Inst, Dallas, TX USA. [Horvath, Keith A.] Suburban Hosp, Ctr Heart, NIH, Bethesda, MD USA. [Geller, Nancy L.] Off Biostatist Res, Bethesda, MD USA. [Miller, Marissa A.] Div Cardiovasc Sci, Bethesda, MD USA. [Ailawadi, Gorav; Kron, Irving L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Gardner, Timothy J.] Ctr Heart & Vasc Hlth, Newark, DE USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu OI Moskowitz, Alan/0000-0002-4412-9450 FU National Heart, Lung, and Blood Institute [U01 HL088942]; National Institute of Neurological Diseases and Stroke, National Institutes of Health; Canadian Institutes of Health Research FX Supported by a cooperative agreement (U01 HL088942) with the National Heart, Lung, and Blood Institute and the National Institute of Neurological Diseases and Stroke, National Institutes of Health, and by the Canadian Institutes of Health Research. NR 43 TC 195 Z9 199 U1 6 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 23 EP 32 DI 10.1056/NEJMoa1312808 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100007 PM 24245543 ER PT J AU Klauer, SG Guo, F Simons-Morton, BG Ouimet, MC Lee, SE Dingus, TA AF Klauer, Sheila G. Guo, Feng Simons-Morton, Bruce G. Ouimet, Marie Claude Lee, Suzanne E. Dingus, Thomas A. TI Distracted Driving and Risk of Road Crashes among Novice and Experienced Drivers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PERFORMANCE; PHONES AB BackgroundDistracted driving attributable to the performance of secondary tasks is a major cause of motor vehicle crashes both among teenagers who are novice drivers and among adults who are experienced drivers. MethodsWe conducted two studies on the relationship between the performance of secondary tasks, including cell-phone use, and the risk of crashes and near-crashes. To facilitate objective assessment, accelerometers, cameras, global positioning systems, and other sensors were installed in the vehicles of 42 newly licensed drivers (16.3 to 17.0 years of age) and 109 adults with more driving experience. ResultsDuring the study periods, 167 crashes and near-crashes among novice drivers and 518 crashes and near-crashes among experienced drivers were identified. The risk of a crash or near-crash among novice drivers increased significantly if they were dialing a cell phone (odds ratio, 8.32; 95% confidence interval [CI], 2.83 to 24.42), reaching for a cell phone (odds ratio, 7.05; 95% CI, 2.64 to 18.83), sending or receiving text messages (odds ratio, 3.87; 95% CI, 1.62 to 9.25), reaching for an object other than a cell phone (odds ratio, 8.00; 95% CI, 3.67 to 17.50), looking at a roadside object (odds ratio, 3.90; 95% CI, 1.72 to 8.81), or eating (odds ratio, 2.99; 95% CI, 1.30 to 6.91). Among experienced drivers, dialing a cell phone was associated with a significantly increased risk of a crash or near-crash (odds ratio, 2.49; 95% CI, 1.38 to 4.54); the risk associated with texting or accessing the Internet was not assessed in this population. The prevalence of high-risk attention to secondary tasks increased over time among novice drivers but not among experienced drivers. ConclusionsThe risk of a crash or near-crash among novice drivers increased with the performance of many secondary tasks, including texting and dialing cell phones. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Highway Traffic Safety Administration.) C1 [Klauer, Sheila G.; Guo, Feng; Lee, Suzanne E.; Dingus, Thomas A.] Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA. [Guo, Feng] Virginia Polytech Inst & State Univ, Dept Stat, Blacksburg, VA 24061 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Ouimet, Marie Claude] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. RP Klauer, SG (reprint author), Virginia Tech, Transportat Inst, 3500 Transportat Res Plaza, Blacksburg, VA 24061 USA. EM cklauer@vtti.vt.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Highway Traffic Safety Administration FX Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Highway Traffic Safety Administration. NR 18 TC 111 Z9 111 U1 10 U2 71 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 54 EP 59 DI 10.1056/NEJMsa1204142 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100010 PM 24382065 ER PT J AU Polizzotto, MN Uldrick, TS Yarchoan, R AF Polizzotto, Mark N. Uldrick, Thomas S. Yarchoan, Robert TI Case 29-2013: An HIV-Positive Man with Dyspnea and Skin Lesions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INFLAMMATORY SYNDROME; DISEASE C1 [Polizzotto, Mark N.; Uldrick, Thomas S.; Yarchoan, Robert] NCI, Bethesda, MD 20892 USA. RP Polizzotto, MN (reprint author), NCI, Bethesda, MD 20892 USA. EM mark.polizzotto@nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 87 EP 88 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100028 PM 24382082 ER PT J AU Prufer, K Racimo, F Patterson, N Jay, F Sankararaman, S Sawyer, S Heinze, A Renaud, G Sudmant, PH de Filippo, C Li, H Mallick, S Dannemann, M Fu, QM Kircher, M Kuhlwilm, M Lachmann, M Meyer, M Ongyerth, M Siebauer, M Theunert, C Tandon, A Moorjani, P Pickrell, J Mullikin, JC Vohr, SH Green, RE Hellmann, I Johnson, PLF Blanche, H Cann, H Kitzman, JO Shendure, J Eichler, EE Lein, ES Bakken, TE Golovanova, LV Doronichev, VB Shunkov, MV Derevianko, AP Viola, B Slatkin, M Reich, D Kelso, J Paabo, S AF Pruefer, Kay Racimo, Fernando Patterson, Nick Jay, Flora Sankararaman, Sriram Sawyer, Susanna Heinze, Anja Renaud, Gabriel Sudmant, Peter H. de Filippo, Cesare Li, Heng Mallick, Swapan Dannemann, Michael Fu, Qiaomei Kircher, Martin Kuhlwilm, Martin Lachmann, Michael Meyer, Matthias Ongyerth, Matthias Siebauer, Michael Theunert, Christoph Tandon, Arti Moorjani, Priya Pickrell, Joseph Mullikin, James C. Vohr, Samuel H. Green, Richard E. Hellmann, Ines Johnson, Philip L. F. Blanche, Helene Cann, Howard Kitzman, Jacob O. Shendure, Jay Eichler, Evan E. Lein, Ed S. Bakken, Trygve E. Golovanova, Liubov V. Doronichev, Vladimir B. Shunkov, Michael V. Derevianko, Anatoli P. Viola, Bence Slatkin, Montgomery Reich, David Kelso, Janet Paeaebo, Svante TI The complete genome sequence of a Neanderthal from the Altai Mountains SO NATURE LA English DT Article ID ANCIENT DNA; POPULATION HISTORY; MEZMAISKAYA CAVE; HUMAN-EVOLUTION; GREAT APE; ADMIXTURE; ANCESTRY; HOMININ; SIBERIA; ASIA AB We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans. C1 [Pruefer, Kay; Sawyer, Susanna; Heinze, Anja; Renaud, Gabriel; de Filippo, Cesare; Dannemann, Michael; Fu, Qiaomei; Kircher, Martin; Kuhlwilm, Martin; Lachmann, Michael; Meyer, Matthias; Ongyerth, Matthias; Siebauer, Michael; Theunert, Christoph; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionare Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany. [Racimo, Fernando; Jay, Flora; Slatkin, Montgomery] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Patterson, Nick; Sankararaman, Sriram; Li, Heng; Mallick, Swapan; Tandon, Arti; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sankararaman, Sriram; Mallick, Swapan; Tandon, Arti; Moorjani, Priya; Pickrell, Joseph; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sudmant, Peter H.; Kircher, Martin; Kitzman, Jacob O.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Fu, Qiaomei] Chinese Acad Sci, Key Lab Vertebrate Evolut & Human Origins, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China. [Mallick, Swapan] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Mallick, Swapan] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Vohr, Samuel H.; Green, Richard E.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Hellmann, Ines] Max F Perutz Labs, Math & Biosci Grp, Campus Vienna Bioctr 5, A-1030 Vienna, Austria. [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Blanche, Helene; Cann, Howard] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA. [Lein, Ed S.; Bakken, Trygve E.] Allen Inst Brain Sci, Seattle, WA 98103 USA. [Golovanova, Liubov V.; Doronichev, Vladimir B.] ANO Lab Prehist 14 Linia 3 11, St Petersburg 199034, Russia. [Shunkov, Michael V.; Derevianko, Anatoli P.] Russian Acad Sci, Inst Archaeol & Ethnog, Palaeolith Dept, Siberian Branch, Novosibirsk 630090, Russia. [Viola, Bence] Max Planck Inst Evolutionare Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany. [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Slatkin, M (reprint author), Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. EM slatkin@berkeley.edu; reich@genetics.med.harvard.edu; paabo@eva.mpg.de RI Li, Heng/D-9344-2011; Derevianko, Anatoly/Q-5975-2016; Shunkov, Mikhail/Q-6576-2016; OI Li, Heng/0000-0003-4874-2874; Derevianko, Anatoly/0000-0003-1156-8331; Shunkov, Mikhail/0000-0003-1388-2308; Bakken, Trygve/0000-0003-3373-7386; Sudmant, Peter/0000-0002-9573-8248; Kuhlwilm, Martin/0000-0002-0115-1797; Shendure, Jay/0000-0002-1516-1865; Viola, Bence/0000-0001-8052-707X; Kircher, Martin/0000-0001-9278-5471 FU NSF [1032255]; NIH [GM100233, HG002385, R01-GM40282]; National Genome Research Institute (NHGRI) [HG006283]; Harvard University Science of the Human Past Program; HHMI International Student Fellowship; Paul G. Allen Family Foundation; Presidential Innovation Fund of the Max Planck Society FX We thank M. Hammer, C. Winkler and W. Klitz for sharing DNA samples; W. Huttner and his group, B. Peter, J. G. Schraiber and M. A. Yang for helpful discussions; and A. Lewis and R. Qiu for technical assistance. N.P. and D. R. are grateful for the chance to discuss these results with Peter Waddell who independently found evidence of a deeply diverged hominin admixing into the Denisova genome. D. R. and E. E. E. are Howard Hughes Medical Institute Investigators. D. R. and N.P. were supported by NSF grant number 1032255 and NIH grant GM100233; E. E. E. by NIH grant HG002385; J. S. by grant HG006283 from the National Genome Research Institute (NHGRI); S. S. by a post-doctoral fellowship from the Harvard University Science of the Human Past Program; F. J. and M. S. in part by a grant from the NIH (R01-GM40282); P. H. S. by an HHMI International Student Fellowship. We thank the team at the NIH Intramural Sequencing Center and Alice Young in particular, for generating some of the sequence reported here. This research was supported in part by the Paul G. Allen Family Foundation. Major funding support came from the Presidential Innovation Fund of the Max Planck Society. NR 46 TC 360 Z9 368 U1 61 U2 429 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 2 PY 2014 VL 505 IS 7481 BP 43 EP + DI 10.1038/nature12886 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282IB UT WOS:000329163300020 PM 24352235 ER PT J AU Ariey, F Witkowski, B Amaratunga, C Beghain, J Langlois, AC Khim, N Kim, S Duru, V Bouchier, C Ma, L Lim, P Leang, R Duong, S Sreng, S Suon, S Chuor, CM Bout, DM Menard, S Rogers, WO Genton, B Fandeur, T Miotto, O Ringwald, P Le Bras, J Berry, A Barale, JC Fairhurst, RM Benoit-Vical, F Mercereau-Puijalon, O Menard, D AF Ariey, Frederic Witkowski, Benoit Amaratunga, Chanaki Beghain, Johann Langlois, Anne-Claire Khim, Nimol Kim, Saorin Duru, Valentine Bouchier, Christiane Ma, Laurence Lim, Pharath Leang, Rithea Duong, Socheat Sreng, Sokunthea Suon, Seila Chuor, Char Meng Bout, Denis Mey Menard, Sandie Rogers, William O. Genton, Blaise Fandeur, Thierry Miotto, Olivo Ringwald, Pascal Le Bras, Jacques Berry, Antoine Barale, Jean-Christophe Fairhurst, Rick M. Benoit-Vical, Franoise Mercereau-Puijalon, Odile Menard, Didier TI A molecular marker of artemisinin-resistant Plasmodium falciparum malaria SO NATURE LA English DT Article ID KELCH-REPEAT SUPERFAMILY; IN-VITRO; PARASITE CLEARANCE; WESTERN CAMBODIA; CHLOROQUINE RESISTANCE; ANTIMALARIAL-DRUGS; POINT MUTATIONS; COPY NUMBER; KEAP1; VIVO AB Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. C1 [Ariey, Frederic; Beghain, Johann; Langlois, Anne-Claire; Fandeur, Thierry; Barale, Jean-Christophe; Mercereau-Puijalon, Odile] Inst Pasteur, Parasite Mol Immunol Unit, F-75724 Paris 15, France. [Ariey, Frederic; Beghain, Johann; Langlois, Anne-Claire; Barale, Jean-Christophe; Mercereau-Puijalon, Odile] CNRS, URA 2581, F-75724 Paris 15, France. [Witkowski, Benoit; Khim, Nimol; Kim, Saorin; Duru, Valentine; Lim, Pharath; Fandeur, Thierry; Menard, Didier] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia. [Amaratunga, Chanaki; Lim, Pharath; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Bouchier, Christiane; Ma, Laurence] Inst Pasteur, Dept Genomes & Genet, F-75724 Paris 15, France. [Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. [Bout, Denis Mey] Natl Ctr Parasitol Entomol & Malaria Control, SSA WHO, Phnom Penh, Cambodia. [Menard, Sandie; Berry, Antoine] Ctr Hosp Univ Toulouse, Serv Parasitol & Mycol, F-31059 Toulouse 9, France. [Rogers, William O.] Naval Med Res Unit 2 Detachment, Phnom Penh, Cambodia. [Genton, Blaise] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland. [Miotto, Olivo] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford OX3 7BN, England. [Miotto, Olivo] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand. [Miotto, Olivo] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Ringwald, Pascal] WHO, Global Malaria Program, CH-1211 Geneva, Switzerland. [Le Bras, Jacques] CHU Bichat Claude Bernard, APHP, PRES Sorbonne Paris Cite, Ctr Natl Reference Paludisme, F-75018 Paris, France. [Benoit-Vical, Franoise] CNRS, Lab Chim Coordinat, UPR8241, F-31077 Toulouse 4, France. [Benoit-Vical, Franoise] Univ Toulouse, UPS, Inst Natl Polytech Toulouse, F-31077 Toulouse 4, France. RP Ariey, F (reprint author), Inst Pasteur, Genet & Genom Insect Vectors Unit, F-75724 Paris 15, France. EM frederic.ariey@pasteur.fr; rfairhurst@niaid.nih.gov; Francoise.Vical@inserm.fr; odile.puijalon@pasteur.fr; dmenard@pasteur-kh.org RI Berry, Antoine/J-9352-2014; Benoit-Vical, Francoise/E-3938-2016; OI Benoit-Vical, Francoise/0000-0002-9468-4823; Miotto, Olivo/0000-0001-8060-6771 FU Global Fund Grant Malaria Program [CAM-607-G10M-CNM3, CAM-S10-G14-M]; Bill and Melinda Gates Foundation; USAID (through the World Health Organization); US DOD Global Epidemic Information System; Intramural Research Program, NIAID, NIH; Banque Natixis; Laboratoire d'Excellence IBEID (Agence Nationale de la Recherche, France); Institut Pasteur, Division International [ACIP A-10-2010]; Institut Pasteur, Division International; French Ministry of Foreign Affairs; Wellcome Trust [098051, 090770/Z/09/Z]; MRC [G0600718]; Rotary Club-Versailles FX We thank the patients and field staff involved in clinical trials and sample collections. We are grateful to the provincial health department directors and other staff of the Cambodian Ministry of Health. Clinical trials and sample collections were supported in part by the Global Fund Grant Malaria Program Rounds 6 (CAM-607-G10M-CNM3) and 9 (CAM-S10-G14-M), the Bill and Melinda Gates Foundation and USAID (through the World Health Organization), the US DOD Global Epidemic Information System, and the Intramural Research Program, NIAID, NIH. Laboratory work was supported by grants from Banque Natixis (to O.M.-P. and D. M.) and Laboratoire d'Excellence IBEID (Agence Nationale de la Recherche, France) and Institut Pasteur, Division International (ACIP A-10-2010). B. W. was supported by a postdoctoral fellowship from Institut Pasteur, Division International; J.B. by an Institut Pasteur Paris Master-Pro fellowship; and D. M. by the French Ministry of Foreign Affairs. We are grateful to the Wellcome Trust Sanger Institute and the MalariaGEN resource centre for sequencing, genotyping and population structure analysis of some Cambodian clinical samples, funded by the Wellcome Trust (098051; 090770/Z/09/Z) and the MRC (G0600718). We thank the Rotary Club-Versailles for funding computer equipment. P. R., D. M. B. and W.O.R. are staff members of the World Health Organization and the US Navy, respectively. They alone are responsible for the views expressed in this publication, and they do not necessarily represent the decisions, policy or views of the World Health Organization or the US Navy. NR 62 TC 434 Z9 448 U1 18 U2 182 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 2 PY 2014 VL 505 IS 7481 BP 50 EP + DI 10.1038/nature12876 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282IB UT WOS:000329163300021 PM 24352242 ER PT J AU Sheikh, V Dersimonian, R Richterman, AG Porter, BO Natarajan, V Burbelo, PD Rupert, A Santich, BH Kardava, L Mican, JM Moir, S Sereti, I AF Sheikh, Virginia Dersimonian, Rebecca Richterman, Aaron G. Porter, Brian O. Natarajan, Ven Burbelo, Peter D. Rupert, Adam Santich, Brian H. Kardava, Lela Mican, JoAnn M. Moir, Susan Sereti, Irini TI Graves' disease as immune reconstitution disease in HIV-positive patients is associated with naive and primary thymic emigrant CD4(+) T-cell recovery SO AIDS LA English DT Article DE Graves' disease; immune reconstitution inflammatory syndrome; immune restoration disease; naive T cells; T-cell receptor excision circles ID ACTIVE ANTIRETROVIRAL THERAPY; AUTOIMMUNE THYROID-DISEASE; INFECTED PATIENTS; B-CELLS; AUTOANTIBODIES; RESTORATION; HAART; FREQUENCIES; IMPAIRMENT AB Objective:Immune restoration disease (IRD) can develop in HIV-infected patients following antiretroviral therapy (ART) initiation as unmasking or paradoxical worsening of opportunistic infections and, rarely, autoimmune phenomena. Although IRD usually occurs in the first months of ART during memory CD4(+) T-cell recovery, Graves' disease occurs as a distinctive late-onset IRD and its pathogenesis is unclear.Design:Seven patients who developed Graves' disease following ART initiation from the primary HIV care clinic at the National Institutes of Health were retrospectively identified and each was matched with two HIV-infected controls based on age, sex, and baseline CD4(+) T-cell count. Laboratory evaluations on stored cryopreserved samples were performed.Methods:Immunophenotyping of peripheral blood mononuclear cells (PBMCs), T-cell receptor excision circle (TREC) analysis in PBMCs, measurement of serum cytokines, and luciferase immunoprecipitation systems (LIPS) analysis for autoimmune antibodies were performed on stored samples for cases and controls at baseline and longitudinally following ART initiation. TSH/thyrotropin receptor (TSH-R) antibody testing was performed on serum from cases. Data were analyzed using nonparametric testing.Results:In comparison with controls, the proportion of naive CD4(+) T cells increased significantly (P=0.0027) in the Graves' disease-IRD patients. TREC/10(6) PBMCs also increased significantly following ART in Graves' disease-IRD patients compared with controls (P=0.0071). Similarly, LIPS analysis demonstrated increases in nonthyroid-related autoantibody titers over time following ART in cases compared with controls.Conclusion:Our data suggest that Graves' disease-IRD, in contrast to early-onset IRD, is associated with naive and primary thymic emigrant CD4(+) T-cell recovery and inappropriate autoantibody production. C1 [Sheikh, Virginia; Richterman, Aaron G.; Porter, Brian O.; Santich, Brian H.; Kardava, Lela; Mican, JoAnn M.; Moir, Susan; Sereti, Irini] NIAID, Bethesda, MD 20892 USA. [Dersimonian, Rebecca] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Natarajan, Ven; Rupert, Adam] Sci Applicat Int Corp Frederick, Frederick Natl Lab, Frederick, MD USA. [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, NIH, Bethesda, MD USA. RP Sheikh, V (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 8C408, Bethesda, MD 20892 USA. EM sheikhv@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Dental and Cranfacial Research (NIDCR); NCI, NIH [HHSN261200800001E] FX This work was supported in part by the Intramural Research Programs of National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Cranfacial Research (NIDCR) and with federal funds from the NCI, NIH under Contract No. HHSN261200800001E. The views expressed in this article are those of the authors and views or policies do not necessarily reflect those of the Department of Health and Human Services, nor does mention of trade names, commercial products. NR 26 TC 10 Z9 10 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2014 VL 28 IS 1 BP 31 EP 39 DI 10.1097/QAD.0000000000000006 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 277KQ UT WOS:000328818400004 PM 23939238 ER PT J AU Cames, C Cournil, A de Vincenzi, I Gaillard, P Meda, N Luchters, S Nduati, R Naidu, K Newell, ML Read, JS Bork, K AF Cames, Cecile Cournil, Amandine de Vincenzi, Isabelle Gaillard, Philippe Meda, Nicolas Luchters, Stanley Nduati, Ruth Naidu, Kevindra Newell, Marie-Louise Read, Jennifer S. Bork, Kirsten CA Kesho Bora Study Grp TI Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting SO AIDS LA English DT Article DE Africa; antiretroviral prophylaxis; body weight change; breastfeeding; HIV infection; overweight ID RANDOMIZED CONTROLLED-TRIAL; TO-CHILD TRANSMISSION; DOSE NEVIRAPINE PROPHYLAXIS; BODY-MASS INDEX; DISEASE PROGRESSION; KESHO BORA; AFRICAN WOMEN; LACTATION; THERAPY; PERCEPTIONS AB Objective:To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites.Methods:HIV-infected pregnant women with CD4(+) cell counts of 200-500cells/l were counselled to choose breastfeeding to 6 months or replacement feeding from delivery. They were randomized to receive perinatal zidovudine and single-dose nevirapine or triple-antiretroviral MTCT prophylaxis until breastfeeding cessation. Mixed-effect linear models were used to compare maternal weight trajectories over time by infant feeding mode. Antiretroviral prophylaxis and BMI at baseline were examined as potential effect modifiers.Results:Among 797 mothers, 620 (78%) initiated breastfeeding. Wasting (BMI <18.5) was rare at baseline (2%), whereas overweight/obesity (BMI25) was common (40%). In the model including all women, breastfeeding was not associated with weight loss up to 6 months, irrespective of baseline BMI and antiretroviral prophylaxis. Triple-antiretroviral prophylaxis was associated with weight gain among replacement-feeding mothers with baseline BMI at least 25 (+0.54kg/month; P<0.0001). In the model including breastfeeding mothers only, triple-antiretroviral prophylaxis was associated with weight gain among mothers with baseline BMI at least 25 who ceased breastfeeding before 3 months postpartum (+0.33kg/month; P=0.03).Conclusion:The results suggest that breastfeeding up to 6 months postpartum is not detrimental for postpartum weight among well nourished HIV-infected mothers at intermediate-disease stage. In the absence of breastfeeding or after weaning, triple-antiretroviral prophylaxis is associated with weight gain among women with high BMI, even after cessation of prophylaxis. C1 [Cames, Cecile; Cournil, Amandine; Bork, Kirsten] IRD, Montpellier, France. [de Vincenzi, Isabelle; Gaillard, Philippe] WHO, CH-1211 Geneva, Switzerland. [Meda, Nicolas] Ctr Muraz, Bobo Dioulasso, Burkina Faso. [Luchters, Stanley] ICRH, Mombasa, Kenya. [Luchters, Stanley] Univ Ghent, Int Ctr Reprod Hlth, B-9000 Ghent, Belgium. [Luchters, Stanley] Burnet Inst, Ctr Int Hlth, Melbourne, Australia. [Nduati, Ruth] Univ Nairobi, Nairobi, Kenya. [Naidu, Kevindra; Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Kwa Zulu, South Africa. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Read, Jennifer S.] NVPO OASH OS DHHS, Washington, DC USA. RP Cames, C (reprint author), CRCF, IRD UM1, UMI233, BP 1386, Dakar 18524, Senegal. EM cecile.cames@ird.fr RI Van de Perre, Philippe/B-9692-2008; OI Van de Perre, Philippe/0000-0002-3912-0427; Bork, Kirsten/0000-0002-5909-7332; Newell, Marie-Louise/0000-0002-1074-7699; Njagi, Ephantus/0000-0002-1484-0241 FU Agence Nationale de Recherches sur le SIDA et les hepatites virales, France; Centers for Disease Control and Prevention, USA; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA; Institut de Recherche pour le Developpement (IRD), Montpellier, France; International Centre for Reproductive Health (ICRH), Ghent University, Ghent, Belgium; Universite Montpellier 1; CHU Montpellier, Laboratoire de Bacteriologie-Virologie, Montpellier, France; Agence Nationale de Recherche sur le SIDA et les hepatites virales (ANRS); Department for International Development (DFID); European and Developing Countries Clinical Trials Partnership (EDCTP); Thrasher Research Fund; Belgian Directorate General for International Cooperation; GlaxoSmithKline Foundation; Centers for Disease Control and Prevention; Eunice Kennedy Shriver National Institute of Child Health and Human Development; UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction; Victorian Operational Infrastructure Support Program; l'Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS); UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP); ANRS; WHO/HRP; Centers for Disease Control and Prevention (CDC); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); EDCTP; UNICEF FX Supporting institutions: (1) Agence Nationale de Recherches sur le SIDA et les hepatites virales, France: Brigitte Bazin and Claire Rekacewicz (Sponsor Representatives); (2) Centers for Disease Control and Prevention, USA: Allan Taylor (Sponsor Representative and Co-Investigator), Nicole Flowers, Michael Thigpen, Mary Glenn Fowler, Denise Jamieson (Co-Investigators); (3) Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA: Lynne M. Mofenson (Sponsor Representative), Jennifer S. Read (Co-Investigator); (4) Institut de Recherche pour le Developpement (IRD), Montpellier, France: Kirsten Bork, Cecile Cames and Amandine Cournil (Nutrition Coordination); (5) International Centre for Reproductive Health (ICRH), Ghent University, Ghent, Belgium: Patricia Claeys, Marleen Temmerman, Stanley Luchters (Sponsor Representatives); (6) Universite Montpellier 1, EA 4205 'Transmission, Pathogenese et Prevention de l'infection par le VIH'; and CHU Montpellier, Laboratoire de Bacteriologie-Virologie, Montpellier, France: Philippe Van de Perre, Pierre Becquart (until December 2006), Vincent Foulongne, Michel Segondy (Laboratory Coordination).; Financial support was provided by Agence Nationale de Recherche sur le SIDA et les hepatites virales (ANRS), Department for International Development (DFID), European and Developing Countries Clinical Trials Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General for International Cooperation, GlaxoSmithKline Foundation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction and the Victorian Operational Infrastructure Support Program.; Funding: The Bobo-Dioulasso site was funded by l'Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS) and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP). The Mombasa sitewas funded by ANRS, WHO/HRP, European and Developing Countries Clinical Trials Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General for International Cooperation. The Nairobi site was funded by the Centers for Disease Control and Prevention (CDC) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through a cooperative agreement. The South-African sites were funded by the Department for International Development (DFID), EDCTP, UNICEF and WHO/HRP. The Nutrition and laboratory coordination were funded by ANRS. The overall coordination and external monitoring was funded by WHO/HRP. NR 33 TC 4 Z9 4 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2014 VL 28 IS 1 BP 85 EP 94 DI 10.1097/01.aids.0000433243.24481.c3 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 277KQ UT WOS:000328818400010 PM 24413262 ER PT S AU Zhang, LB Ma, WJ Chen, L Zhang, S AF Zhang Liangbin Ma Wenjun Chen Li Zhang Su BE Yuan, B Ruan, Q Tang, X TI Research on Detection of Prostate Cancer MR Images based on Information Fusion SO 2014 12TH INTERNATIONAL CONFERENCE ON SIGNAL PROCESSING (ICSP) SE International Conference on Signal Processing LA English DT Proceedings Paper CT 12th IEEE International Conference on Signal Processing (ICSP) CY OCT 19-23, 2014 CL HangZhou, PEOPLES R CHINA SP IEEE, Inst Engn & Technol, URSI, Chinese Inst Elect, Int Conf Signal Proc, Beijing Jiaotong Univ, CIE Signal Proc Soc DE prostate cancer; magnetic resonance imaging; information fusion ID COMPUTER-AIDED DIAGNOSIS AB The study evaluated a method of computer-assisted diagnosis (CAD) by introducing information fusion into the clinical diagnosis of prostate cancer. Based on the multi-parameter magnetic resonance imaging (MRI) including T2-weighed, diffusion-weighed, and dynamic contrast enhanced,VERI, image fusion was applied on the pixel and decision levels, respectively. Results showed that fusion on the decision level obtained superior results in detecting prostate cancer and showing the distribution of benign and malignant tumors, thus, demonstrating its potential for CAD. Several information fusion algorithms were compared using MRI to develop an appropriate method for prostate cancer diagnosis. C1 [Zhang Liangbin; Ma Wenjun; Zhang Su] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China. [Chen Li] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Zhang, LB (reprint author), Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China. EM iuhuyO120@126.com; marsinsider@foxmail.com; ahli1981@gmail.com; suzhang@sjtu.edu.cn NR 8 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2164-5221 BN 978-1-4799-2186-7 J9 INT CONF SIGN PROCES PY 2014 BP 1094 EP 1098 PG 5 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BD9XB UT WOS:000365529500214 ER PT J AU Niciu, MJ Sinclair, CM Zarate, CA Shelton, RC AF Niciu, Mark J. Sinclair, Courtney M. Zarate, Carlos A., Jr. Shelton, Richard C. BA Gabbard, GO BF Gabbard, GO TI Pharmacological and Somatic Treatments for Major Depressive Disorder SO GABBARD'S TREATMENTS OF PSYCHIATRIC DISORDERS, 5TH EDITION LA English DT Article; Book Chapter ID TREATMENT-RESISTANT DEPRESSION; D-ASPARTATE ANTAGONIST; CO-MED TRIAL; REUPTAKE INHIBITOR ANTIDEPRESSANTS; VORTIOXETINE LU AA21004; S-ADENOSYL METHIONINE; LONG-TERM OUTCOMES; 5 MG VORTIOXETINE; STAR-ASTERISK-D; DOUBLE-BLIND C1 [Niciu, Mark J.; Sinclair, Courtney M.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Zarate, Carlos A., Jr.] NIMH, Sect Neurobiol & Treatment Mood Disorders, Div Intramural Res Program, NIH,Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Shelton, Richard C.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Res, Birmingham, AL 35294 USA. RP Niciu, MJ (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. RI Niciu, Mark/J-1766-2014 OI Niciu, Mark/0000-0002-5612-3021 NR 90 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-442-3 PY 2014 BP 275 EP 301 PG 27 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD9FX UT WOS:000364632600018 ER PT B AU Dietz, BM Bolton, JL AF Dietz, Birgit M. Bolton, Judy L. BE Kong, ANT TI Anti-Inflammatory Botanical Dietary Supplements for Women's Health Role in Breast Cancer Prevention? SO INFLAMMATION, OXIDATIVE STRESS, AND CANCER: DIETARY APPROACHES FOR CANCER PREVENTION LA English DT Article; Book Chapter ID NF-KAPPA-B; CIMICIFUGA-RACEMOSA EXTRACT; ESTROGEN-RECEPTOR-BETA; RANDOMIZED CONTROLLED-TRIAL; CLOVER TRIFOLIUM-PRATENSE; HOPS HUMULUS-LUPULUS; SPRAGUE-DAWLEY RATS; INDUCED DNA-DAMAGE; ALLEVIATE MENOPAUSAL DISCOMFORTS; MAMMARY EPITHELIAL-CELLS C1 [Dietz, Birgit M.; Bolton, Judy L.] Univ Illinois, Dept Med Chem & Pharmacognosy, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL USA. RP Dietz, BM (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL USA. NR 167 TC 1 Z9 1 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-0371-7; 978-1-4665-0370-0 PY 2014 BP 529 EP 548 PG 20 WC Oncology; Chemistry, Medicinal; Nutrition & Dietetics SC Oncology; Pharmacology & Pharmacy; Nutrition & Dietetics GA BE0EK UT WOS:000365906100029 ER PT B AU Chen, A Acharya, A Setser, A AF Chen, Alice Acharya, Asha Setser, Ann BE Lacouture, ME TI Grading Dermatologic Adverse Events in Clinical Trials Using CTCAE v4.0 SO DERMATOLOGIC PRINCIPLES AND PRACTICE IN ONCOLOGY: CONDITIONS OF THE SKIN, HAIR, AND NAILS IN CANCER PATIENTS LA English DT Article; Book Chapter ID RENAL-CELL CARCINOMA; LUNG-CANCER; PHASE-I; ERLOTINIB; CETUXIMAB; SORAFENIB; EYELASHES; TOXICITY; RASH C1 [Chen, Alice] NCI, Canc Therapy Evaluat Program, Rockville, MD 20850 USA. [Acharya, Asha] Tech Resources Int Inc, Bethesda, MD USA. [Setser, Ann] Setser Hlth Consulting LLC, Chesterfield, MO USA. RP Chen, A (reprint author), NCI, Canc Therapy Evaluat Program, Rockville, MD 20850 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-59063-8; 978-0-470-62188-2 PY 2014 BP 47 EP 59 PG 13 WC Oncology; Dermatology SC Oncology; Dermatology GA BD7EO UT WOS:000362961900006 ER PT B AU Chu, EY Kong, HH AF Chu, Emily Y. Kong, Heidi H. BE Lacouture, ME TI Antimetabolite Reactions SO DERMATOLOGIC PRINCIPLES AND PRACTICE IN ONCOLOGY: CONDITIONS OF THE SKIN, HAIR, AND NAILS IN CANCER PATIENTS LA English DT Article; Book Chapter ID RADIATION RECALL DERMATITIS; HIGH-DOSE METHOTREXATE; CELL LUNG-CANCER; CHRONIC LYMPHOCYTIC-LEUKEMIA; NEUTROPHILIC ECCRINE HIDRADENITIS; INFLAMMATORY-BOWEL-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACRAL ERYTHEMA SECONDARY; VERSUS-HOST-DISEASE; HAND-FOOT SYNDROME C1 [Chu, Emily Y.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kong, Heidi H.] NCI, Clin Res Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Chu, EY (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 116 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-59063-8; 978-0-470-62188-2 PY 2014 BP 160 EP 169 PG 10 WC Oncology; Dermatology SC Oncology; Dermatology GA BD7EO UT WOS:000362961900016 ER PT B AU Wexler, P Berman, F Nance, P Parker, A Patterson, J AF Wexler, Philip Berman, Fred Nance, Patricia Parker, Ann Patterson, Jacqueline BE Hayes, AW Kruger, CL TI The Information Infrastructure of Toxicology SO HAYES' PRINCIPLES AND METHODS OF TOXICOLOGY, 6TH EDITION LA English DT Article; Book Chapter DE Information; Informatics; Databases; Web Resources; Computer Searching ID ENVIRONMENTAL-PROTECTION-AGENCY; COMPUTATIONAL TOXICOLOGY; RESOURCES; RISK C1 [Wexler, Philip] Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20894 USA. [Berman, Fred] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Toxicol Informat Ctr, Portland, OR 97201 USA. [Nance, Patricia; Parker, Ann; Patterson, Jacqueline] Toxicol Excellence Risk Assessment, Cincinnati, OH USA. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20894 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84214-537-1; 978-1-84214-536-4 PY 2014 BP 597 EP 618 D2 10.1201/b17359 PG 22 WC Toxicology SC Toxicology GA BD7FA UT WOS:000362973800014 ER PT B AU Stokes, WS AF Stokes, William S. BE Hayes, AW Kruger, CL TI Validation and Regulatory Acceptance of Toxicological Testing Methods and Strategies SO HAYES' PRINCIPLES AND METHODS OF TOXICOLOGY, 6TH EDITION LA English DT Article; Book Chapter DE Alternative methods; Safety testing; Validation; Regulatory acceptance; Allergic contact dermatitis testing; Dermal corrosivity testing ID LYMPH-NODE ASSAY; SCREENING CONTACT ALLERGENS; ISOTOPIC END-POINT; ICCVAM EVALUATION; ALTERNATIVE METHODS; SKIN SENSITIZATION; PEPTIDE REACTIVITY; TASK-FORCE; ECVAM; CHEMICALS C1 [Stokes, William S.] US PHS, Washington, DC USA. [Stokes, William S.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Stokes, William S.] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA. NR 107 TC 0 Z9 0 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84214-537-1; 978-1-84214-536-4 PY 2014 BP 1081 EP 1115 D2 10.1201/b17359 PG 35 WC Toxicology SC Toxicology GA BD7FA UT WOS:000362973800022 ER PT B AU Potter, MP Hwang, S Bostic, JQ AF Potter, Mona Patel Hwang, Soonjo Bostic, Jeff Q. BE Reece, RM Hanson, RF Sargent, J TI The Abused Student Cornered School Bullying amidst Trauma SO TREATMENT OF CHILD ABUSE: COMMON GROUND FOR MENTAL HEALTH, MEDICAL, AND LEGAL PRACTITIONERS, 2ND EDITION LA English DT Article; Book Chapter ID CHILDRENS PEER GROUPS; POLY-VICTIMIZATION; PARENTAL MALTREATMENT; MIDDLE SCHOOL; ADOLESCENTS; HEALTH; EMOTION; PROGRAM; RISK; INTERVENTION C1 [Potter, Mona Patel] McLean Hosp, Child & Adolescent Psychiat, Belmont, MA 02178 USA. [Potter, Mona Patel] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hwang, Soonjo] Massachusetts Gen Hosp, NIH, NIMH, Dept Psychiat, Boston, MA 02114 USA. [Bostic, Jeff Q.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Potter, MP (reprint author), McLean Hosp, Child & Adolescent Psychiat, 115 Mill St, Belmont, MA 02178 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA 2715 N CHARLES ST, BALTIMORE, MD 21218-4319 USA BN 978-1-4214-1273-3; 978-1-4214-1274-0; 978-1-4214-1272-6 PY 2014 BP 139 EP 147 PG 9 WC Public, Environmental & Occupational Health; Medicine, Legal SC Public, Environmental & Occupational Health; Legal Medicine GA BD6NU UT WOS:000362429500016 ER PT B AU Altman, BM Lollar, DJ Rasch, EK AF Altman, Barbara M. Lollar, Donald J. Rasch, Elizabeth K. BE Altman, BM Barnartt, SN TI THE EXPERIENCE OF ENVIRONMENTAL BARRIERS AMONG ADULTS WITH DISABILITIES: A NATIONAL DESCRIPTION SO ENVIRONMENTAL CONTEXTS AND DISABILITY SE Research in Social Science and Disability LA English DT Article; Book Chapter DE Disability; environment AB Purpose In recent years, recognition of environmental influences in public health has expanded to include more components of the environment such as the built environment, attitudes, and public policies. This environmental attention has addressed the need for healthier housing, schools, roads, and work sites, as some examples. Paralleling the development of awareness of the impact of environment on health and health behaviors, the influence of the environment and its contribution to the experience of disability has become more apparent. This national descriptive analysis of environmental barriers contributes to our understanding of the extent of environmental considerations for the entire U.S. adult population, not just older individuals, and will document those problems for those with self-reported functional limitations (i.e., disability). Design/methodology/approach This analysis uses the 2002 National Health Interview data to examine physical, social, and policy barriers experienced by the U.S. national population of adults age 18 or over. Focusing specifically on those who report a physical, activity, participation, or mental health limitation, the experience of barriers in the home, workplace, school, and the community is examined using descriptive analyses. Findings Results indicate that approximately 11% of the population with disabilities and 2% of the nondisabled adult population experience barriers in their daily lives. Severity of limitations and poor health status among those with disabilities increase the experience of barriers. The only sociodemographic factor related to reporting barriers was income. Depending on the kind of limitation, up to 28.6% of the population with disabilities experience barriers. The two most frequently reported types of barriers were building design and attitudes of other people. Social implications This analysis provides an indication of how the environment is experienced by adults with disabilities and identifies perceived barriers found in the home, the work/school environment and the community. It starts to provide a baseline for understanding of the environment as experienced by persons with disabilities and suggests the most pressing areas for attention. Originality/value To our knowledge, this is among the first nationally representative analysis of barriers that interfere with daily activities experienced by adults in the United States. It highlights the experience of adults with disabilities and describes numerous types of potential barriers. C1 [Altman, Barbara M.] Univ Maryland, Dept Sociol, Baltimore, MD 21201 USA. [Lollar, Donald J.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Rasch, Elizabeth K.] NIH, Epidemiol & Biostat Sect, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Altman, BM (reprint author), Univ Maryland, Dept Sociol, Baltimore, MD 21201 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND BN 978-1-78441-262-3; 978-1-78441-263-0 J9 RES SOC SCI DISABIL PY 2014 VL 8 BP 33 EP 53 DI 10.1108/S1479-354720140000008003 D2 10.1108/S1479-354720148 PG 21 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA BD4JM UT WOS:000360846600003 ER PT S AU Greenberg, J Murillo, A Ogletree, A Boyles, R Martin, N Romeo, C AF Greenberg, Jane Murillo, Angela Ogletree, Adrian Boyles, Rebecca Martin, Negin Romeo, Charles BE Closs, S Studer, R Garoufallou, E Sicilia, MA TI Metadata Capital: Automating Metadata Workflows in the NIEHS Viral Vector Core Laboratory SO METADATA AND SEMANTICS RESEARCH, MTSR 2014 SE Communications in Computer and Information Science LA English DT Proceedings Paper CT 8th Metadata and Semantics Research Conference (MTSR) CY NOV 27-29, 2014 CL Karlsruhe Univ Appl Sci, Karlsruhe, GERMANY HO Karlsruhe Univ Appl Sci DE Metadata Capital; Viral Vector Core Laboratory; qPCR data; Workflows; E-Science; iRODS AB This paper presents research examining metadata capital in the context of the Viral Vector Core Laboratory at the National Institute of Environmental Health Sciences (NIEHS). Methods include collaborative workflow modeling and a metadata analysis. Models of the laboratory's workflow and metadata activity are generated to identify potential opportunities for defining microservices that may be supported by iRODS rules. Generic iRODS rules are also shared along with images of the iRODS prototype. The discussion includes an exploration of a modified capital sigma equation to understand metadata as an asset. The work aims to raise awareness of metadata as an asset and to incentivize investment in metadata R&D. C1 [Greenberg, Jane; Murillo, Angela; Ogletree, Adrian] Drexel Univ, CCI, MRC, Philadelphia, PA 19104 USA. [Murillo, Angela] Univ N Carolina, SILS, Chapel Hill, NC USA. [Boyles, Rebecca] NIEHS, Off Sci Informat Management, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Martin, Negin; Romeo, Charles] NIEHS, Neurobiol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Greenberg, J (reprint author), Drexel Univ, CCI, MRC, Philadelphia, PA 19104 USA. EM janeg@drexel.edu; amurillo@email.unc.edu; aogletree@drexel.edu; rebecca.boyles@nih.gov; martin@niehs.nih.gov; romeoc@niehs.nih.gov OI Ogletree, Adrian/0000-0002-1059-8232; Boyles, Rebecca/0000-0003-0073-6854; Martin, Negin/0000-0003-3166-8989 NR 23 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1865-0929 BN 978-3-319-13674-5; 978-3-319-13673-8 J9 COMM COM INF SC PY 2014 VL 478 BP 1 EP 13 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BD7LP UT WOS:000363269900001 ER PT B AU Chatterjee, N AF Chatterjee, Nilanjan BE Lin, X Genest, C Banks, DL Molenberghs, G Scott, DW Wang, JL TI The road travelled: From statistician to statistical scientist SO PAST, PRESENT, AND FUTURE OF STATISTICAL SCIENCE LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INDEPENDENCE; BREAST-CANCER; ESTIMATING PENETRANCE; KIN-COHORT; RISK; LOCI; SUSCEPTIBILITY; ESTIMATOR; VARIANTS AB In this chapter, I will attempt to describe how a series of problems in statistical genetics, starting from a project about estimation of risk for BRCA1/2 mutation carriers, have driven a major part of my research at the National Cancer Institute over the last fourteen years. I try to share some of the statistical and scientific perspectives in this field that I have developed over the years during which I myself have transformed from a theoretical statistician to a statistical scientist. I hope my experience would draw the attention of other statisticians, especially young researchers who have perceived strength in statistical theory but are keen on using their knowledge to advance science, about the tremendous opportunity that lies ahead. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-0498-8; 978-1-4822-0496-4 PY 2014 BP 177 EP 187 D2 10.1201/b16720 PG 11 WC Education, Scientific Disciplines; History & Philosophy Of Science; Statistics & Probability SC Education & Educational Research; History & Philosophy of Science; Mathematics GA BD5RD UT WOS:000361750600018 ER PT B AU Blaney, JE Johnson, RF AF Blaney, Joseph E. Johnson, Reed F. BE Liu, D TI Monkeypox Virus SO MANUAL OF SECURITY SENSITIVE MICROBES AND TOXINS LA English DT Article; Book Chapter ID REAL-TIME PCR; EXTRACELLULAR ENVELOPED VIRUS; ANTIPOXVIRUS COMPOUND ST-246; ATTENUATED SMALLPOX VACCINE; FAMILY TYROSINE KINASES; POXVIRUS INFECTIONS; DNA-POLYMERASE; COWPOX VIRUS; F13L PROTEIN; CONGO BASIN C1 [Blaney, Joseph E.; Johnson, Reed F.] NIAID, Emerging Viral Pathogens Sect, NIH, Ft Detrick, MD 21702 USA. RP Blaney, JE (reprint author), NIAID, Emerging Viral Pathogens Sect, NIH, Ft Detrick, MD 21702 USA. NR 118 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-5398-9; 978-1-4665-5396-5 PY 2014 BP 179 EP 192 D2 10.1201/b16752 PG 14 WC Infectious Diseases; Microbiology; Toxicology SC Infectious Diseases; Microbiology; Toxicology GA BD7GW UT WOS:000363061700017 ER PT B AU Ruzek, D Holbrook, MR Yakimenko, VV Karan, LS Tkachev, SE AF Ruzek, Daniel Holbrook, Michael R. Yakimenko, Valeriy V. Karan, Lyudmila S. Tkachev, Sergey E. BE Liu, D TI Omsk Hemorrhagic Fever Virus SO MANUAL OF SECURITY SENSITIVE MICROBES AND TOXINS LA English DT Article; Book Chapter ID TICK-BORNE FLAVIVIRUS; ANTIGENIC RELATIONSHIPS; ENCEPHALITIS; VACCINES; HUMANS; TESTS C1 [Ruzek, Daniel] Vet Res Inst, Dept Virol, CS-62132 Brno, Czech Republic. [Ruzek, Daniel] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. [Holbrook, Michael R.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Yakimenko, Valeriy V.] Omsk Res Inst Nat Foci Infect, Omsk, Russia. [Karan, Lyudmila S.] Minist Publ Hlth Russia, Cent Res Inst Epidemiol, Lab Epidemiol Zoonoses, Moscow, Russia. [Tkachev, Sergey E.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. RP Ruzek, D (reprint author), Vet Res Inst, Dept Virol, CS-62132 Brno, Czech Republic. NR 48 TC 0 Z9 0 U1 1 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-5398-9; 978-1-4665-5396-5 PY 2014 BP 193 EP 200 D2 10.1201/b16752 PG 8 WC Infectious Diseases; Microbiology; Toxicology SC Infectious Diseases; Microbiology; Toxicology GA BD7GW UT WOS:000363061700018 ER PT S AU Yakel, JL AF Yakel, Jerrel L. BE Lester, RAJ TI Functional Distribution and Regulation of Neuronal Nicotinic ACh Receptors in the Mammalian Brain SO NICOTINIC RECEPTORS SE Receptors Series LA English DT Article; Book Chapter DE Acetylcholine; Synaptic plasticity; Neurotransmitter; Allosteric modulation; Neurological disease ID POSITIVE ALLOSTERIC MODULATOR; LONG-TERM POTENTIATION; HIPPOCAMPAL SYNAPTIC PLASTICITY; CENTRAL-NERVOUS-SYSTEM; STRATUM-RADIATUM INTERNEURONS; REPORTER MUTATION APPROACH; CENTRAL CHOLINERGIC SYSTEM; RAT STRIATAL SYNAPTOSOMES; MIDBRAIN DOPAMINE NEURONS; ACETYLCHOLINE-RECEPTORS AB The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability throughout the nervous system by acting on the cys-loop cation-conducting ligand-gated nicotinic ACh receptor channels (nAChRs). These receptors are widely distributed throughout the nervous system, being expressed on neurons and nonneuronal cells where they participate in a variety of physiological responses. In the mammalian brain, nine different subunits have been discovered thus far, which assemble into pentameric complexes with much diversity. The neuronal subtypes of these receptors, primarily composed of the alpha 7 and non-alpha 7 subtypes (e.g. alpha 4 beta 2 and alpha 3 beta 4), are involved in a variety of neurobehavioral processes such as anxiety, the central processing of pain, food intake, nicotine-seeking behavior, and cognitive functions. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders and diseases including (but not limited to) Alzheimer's and Parkinson's diseases, schizophrenia, and epilepsy. Here I will briefly discuss the functional makeup and expression of nAChRs in the mammalian brain, and the role that they play in these various circuits, in normal function, and in disease. C1 NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov NR 224 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1048-6909 BN 978-1-4939-1167-7; 978-1-4939-1166-0 J9 RECEPT SER JI Recept. Ser. PY 2014 VL 26 BP 93 EP 114 DI 10.1007/978-1-4939-1167-7_5 D2 10.1007/978-1-4939-1167-7 PG 22 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BD7BJ UT WOS:000362845200006 ER PT J AU Spurdle, AB Couch, FJ Parsons, MT McGuffog, L Barrowdale, D Bolla, MK Wang, Q Healey, S Schmutzler, RK Wappenschmidt, B Rhiem, K Hahnen, E Engel, C Meindl, A Ditsch, N Arnold, N Plendl, H Niederacher, D Sutter, C Wang-Gohrke, S Steinemann, D Preisler-Adams, S Kast, K Varon-Mateeva, R Ellis, S Frost, D Platte, R Perkins, J Evans, DG Izatt, L Eeles, R Adlard, J Davidson, R Cole, T Scuvera, G Manoukian, S Bonanni, B Mariette, F Fortuzzi, S Viel, A Pasini, B Papi, L Varesco, L Balleine, R Nathanson, KL Domchek, SM Offitt, K Jakubowska, A Lindor, N Thomassen, M Jensen, UB Rantala, J Borg, A Andrulis, IL Miron, A Hansen, TVO Caldes, T Neuhausen, SL Toland, AE Nevanlinna, H Montagna, M Garber, J Godwin, AK Osorio, A Factor, RE Terry, MB Rebbeck, TR Karlan, BY Southey, M Rashid, MU Tung, N Pharoah, PDP Blows, FM Dunning, AM Provenzano, E Hall, P Czene, K Schmidt, MK Broeks, A Cornelissen, S Verhoef, S Fasching, PA Beckmann, MW Ekici, AB Slamon, DJ Bojesen, SE Nordestgaard, BG Nielsen, SF Flyger, H Chang-Claude, J Flesch-Janys, D Rudolph, A Seibold, P Aittomaki, K Muranen, TA Heikkila, P Blomqvist, C Figueroa, J Chanock, SJ Brinton, L Lissowska, J Olson, JE Pankratz, VS John, EM Whittemore, AS West, DW Hamann, U Torres, D Ulmer, HU Rudiger, T Devilee, P Tollenaar, RAEM Seynaeve, C Van Asperen, CJ Eccles, DM Tapper, WJ Durcan, L Jones, L Peto, J dos-Santos-Silva, I Fletcher, O Johnson, N Dwek, M Swann, R Bane, AL Glendon, G Mulligan, AM Giles, GG Milne, RL Baglietto, L McLean, C Carpenter, J Clarke, C Scott, R Brauch, H Bruning, T Ko, YD Cox, A Cross, SS Reed, MWR Lubinski, J Jaworska-Bieniek, K Durda, K Gronwald, J Dork, T Bogdanova, N Park-Simon, TW Hillemanns, P Haiman, CA Henderson, BE Schumacher, F Le Marchand, L Burwinkel, B Marme, F Surovy, H Yang, R Anton-Culver, H Ziogas, A Hooning, MJ Collee, JM Martens, JWM Tilanus-Linthorst, MMA Brenner, H Dieffenbach, AK Arndt, V Stegmaier, C Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Lindblom, A Margolin, S Joseph, V Robson, M Rau-Murthy, R Gonzalez-Neira, A Arias, JI Zamora, P Benitez, J Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Peterlongo, P Zaffaroni, D Barile, M Capra, F Radice, P Teo, SH Easton, DF Antoniou, AC Chenevix-Trench, G Goldgar, DE AF Spurdle, Amanda B. Couch, Fergus J. Parsons, Michael T. McGuffog, Lesley Barrowdale, Daniel Bolla, Manjeet K. Wang, Qin Healey, Sue Schmutzler, Rita Katharina Wappenschmidt, Barbara Rhiem, Kerstin Hahnen, Eric Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hansjoerg Niederacher, Dieter Sutter, Christian Wang-Gohrke, Shan Steinemann, Doris Preisler-Adams, Sabine Kast, Karin Varon-Mateeva, Raymonda Ellis, Steve Frost, Debra Platte, Radka Perkins, Jo Evans, D. Gareth Izatt, Louise Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Scuvera, Giulietta Manoukian, Siranoush Bonanni, Bernardo Mariette, Frederique Fortuzzi, Stefano Viel, Alessandra Pasini, Barbara Papi, Laura Varesco, Liliana Balleine, Rosemary Nathanson, Katherine L. Domchek, Susan M. Offitt, Kenneth Jakubowska, Anna Lindor, Noralane Thomassen, Mads Jensen, Uffe Birk Rantala, Johanna Borg, Ake Andrulis, Irene L. Miron, Alexander Hansen, Thomas V. O. Caldes, Trinidad Neuhausen, Susan L. Toland, Amanda E. Nevanlinna, Heli Montagna, Marco Garber, Judy Godwin, Andrew K. Osorio, Ana Factor, Rachel E. Terry, Mary B. Rebbeck, Timothy R. Karlan, Beth Y. Southey, Melissa Rashid, Muhammad Usman Tung, Nadine Pharoah, Paul D. P. Blows, Fiona M. Dunning, Alison M. Provenzano, Elena Hall, Per Czene, Kamila Schmidt, Marjanka K. Broeks, Annegien Cornelissen, Sten Verhoef, Senno Fasching, Peter A. Beckmann, Matthias W. Ekici, Arif B. Slamon, Dennis J. Bojesen, Stig E. Nordestgaard, Borge G. Nielsen, Sune F. Flyger, Henrik Chang-Claude, Jenny Flesch-Janys, Dieter Rudolph, Anja Seibold, Petra Aittomaki, Kristiina Muranen, Taru A. Heikkila, Paivi Blomqvist, Carl Figueroa, Jonine Chanock, Stephen J. Brinton, Louise Lissowska, Jolanta Olson, Janet E. Pankratz, Vernon S. John, Esther M. Whittemore, Alice S. West, Dee W. Hamann, Ute Torres, Diana Ulmer, Hans Ulrich Rudiger, Thomas Devilee, Peter Tollenaar, Robert A. E. M. Seynaeve, Caroline Van Asperen, Christi J. Eccles, Diana M. Tapper, William J. Durcan, Lorraine Jones, Louise Peto, Julian dos-Santos-Silva, Isabel Fletcher, Olivia Johnson, Nichola Dwek, Miriam Swann, Ruth Bane, Anita L. Glendon, Gord Mulligan, Anna M. Giles, Graham G. Milne, Roger L. Baglietto, Laura McLean, Catriona Carpenter, Jane Clarke, Christine Scott, Rodney Brauch, Hiltrud Bruning, Thomas Ko, Yon-Dschun Cox, Angela Cross, Simon S. Reed, Malcolm W. R. Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Gronwald, Jacek Dork, Thilo Bogdanova, Natalia Park-Simon, Tjoung-Won Hillemanns, Peter Haiman, Christopher A. Henderson, Brian E. Schumacher, Fredrick Le Marchand, Loic Burwinkel, Barbara Marme, Frederik Surovy, Harald Yang, Rongxi Anton-Culver, Hoda Ziogas, Argyrios Hooning, Maartje J. Collee, J. Margriet Martens, John W. M. Tilanus-Linthorst, Madeleine M. A. Brenner, Hermann Dieffenbach, Aida Karina Arndt, Volke Stegmaier, Christa Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Lindblom, Annika Margolin, Sara Joseph, Vijai Robson, Mark Rau-Murthy, Rohini Gonzalez-Neira, Anna Arias, Jose Ignacio Zamora, Pilar Benitez, Javier Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Peterlongo, Paolo Zaffaroni, Daniela Barile, Monica Capra, Fabio Radice, Paolo Teo, Soo H. Easton, Douglas F. Antoniou, Antonis C. Chenevix-Trench, Georgia Goldgar, David E. CA ABCTB Investigators EMBRACE Group GENICA Network HEBON Group kConFab Investigators TI Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia SO BREAST CANCER RESEARCH LA English DT Article ID DNA-SEQUENCE VARIANTS; UNKNOWN CLINICAL-SIGNIFICANCE; ESTROGEN-RECEPTOR; GERMLINE MUTATIONS; BASAL PHENOTYPE; BRCA1-MUTATION CARRIERS; ASSOCIATION CONSORTIUM; PATHOLOGICAL FEATURES; OVARIAN CANCERS; TUMOR PATHOLOGY AB Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). Conclusions: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management. C1 [Spurdle, Amanda B.; Parsons, Michael T.; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [McGuffog, Lesley; Barrowdale, Daniel; Bolla, Manjeet K.; Wang, Qin; Ellis, Steve; Frost, Debra; Platte, Radka; Perkins, Jo; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Wang, Qin; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB2 1TN, England. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Cologne, Ctr Hereditary Breast & Ovarian Canc, CIO, Cologne, Germany. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Cologne, CMMC, Fac Med, Cologne, Germany. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Hosp Cologne, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-81675 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Gynaecol & Obstet, D-80337 Munich, Germany. [Plendl, Hansjoerg] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany. [Plendl, Hansjoerg] Univ Med Ctr Schleswig Holstein, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Gynaecol & Obstet, Dusseldorf, Germany. [Sutter, Christian] Univ Hosp Heidelberg, Inst Human Genet, D-69120 Heidelberg, Germany. [Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Gynaecol & Obstet, D-89081 Ulm, Germany. [Steinemann, Doris] Hannover Med Sch, Inst Cell & Mol Pathol, Hannover, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, Munster, Germany. [Kast, Karin] Tech Univ Dresden, Dept Gynecol & Obstet, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Varon-Mateeva, Raymonda] Campus Virchov Klinikum, Inst Human Genet, Charite Berlin, Germany. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Adlard, Julian] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Southern Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, Scotland. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Scuvera, Giulietta; Manoukian, Siranoush; Zaffaroni, Daniela] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, I-20133 Milan, Italy. [Bonanni, Bernardo; Barile, Monica] IEO, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Mariette, Frederique; Fortuzzi, Stefano; Peterlongo, Paolo; Capra, Fabio] Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy. [Mariette, Frederique; Fortuzzi, Stefano; Capra, Fabio] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Viel, Alessandra] CRO Aviano Natl Canc Inst, Div Expt Oncol 1, I-33081 Aviano, PN, Italy. [Pasini, Barbara] Univ Turin, Dept Med Sci, I-10126 Turin, Italy. [Pasini, Barbara] AOU Citta Salute & Sci, I-10126 Turin, Italy. [Papi, Laura] Univ Florence, Unit Med Genet, Dept Biomed Expt & Clin Sci, I-50139 Florence, Italy. [Varesco, Liliana] IRCCS AOU San Martino IST Ist Nazl Ric Canc, Unit Hereditary Canc, I-16132 Genoa, Italy. [Balleine, Rosemary] Univ Sydney, Western Sydney & Nepean Blue Mt Local Hlth Dist, Westmead Millennium Inst Med Res, Westmead, NSW 2145, Australia. [Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Offitt, Kenneth; Joseph, Vijai; Robson, Mark; Rau-Murthy, Rohini] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY 10021 USA. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Gronwald, Jacek] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland. [Lindor, Noralane] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense C, Denmark. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark. [Rantala, Johanna] Karolinska Univ Hosp L5 03, Dept Clin Genet, S-17176 Stockholm, Sweden. [Borg, Ake] Lund Univ, Dept Oncol, Clin Sci, Lund, Sweden. [Borg, Ake] Skane Univ Hosp, Lund, Sweden. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Miron, Alexander] Case Western Reserve Univ, Dept Genet & Genome Serv, Sch Med, Cleveland, OH 44106 USA. [Hansen, Thomas V. O.] Univ Copenhagen Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, IdISSC, Madrid, Spain. [Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Dept Internal Med, Comprehens Canc Ctr, Columbus, OH USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Dept Mol Virol Immunol & Med Genet, Comprehens Canc Ctr, Columbus, OH USA. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland. [Montagna, Marco] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Garber, Judy] Dana Farber Canc Inst, Boston, MA USA. [Godwin, Andrew K.] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Kansas City, KS USA. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Human Canc Genet Program, Madrid 28029, Spain. [Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid, Spain. [Factor, Rachel E.] Univ Utah, Dept Pathol, Hlth Sci Ctr, Salt Lake City, UT 84132 USA. [Terry, Mary B.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA USA. [Southey, Melissa] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Parkville, Vic, Australia. [Rashid, Muhammad Usman; Hamann, Ute; Torres, Diana] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Rashid, Muhammad Usman] Shaukat Khanum Mem Canc Hosp & Res Ctr SKMCH & RC, Dept Basic Sci, Johar, Pakistan. [Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Blows, Fiona M.; Dunning, Alison M.; Provenzano, Elena] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Verhoef, Senno] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Fasching, Peter A.; Slamon, Dennis J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Breast Ctr Franconia, Univ Hosp Erlangen,Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Slamon, Dennis J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen Hosp, Copenhagen Gen Populat Study, Herlev Hosp, DK-2730 Herlev, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen Hosp, Dept Clin Biochem, Herlev Hosp, DK-2730 Herlev, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen N, Denmark. [Flyger, Henrik] Univ Copenhagen Hosp, Dept Breast Surg, Herlev Hosp, DK-2730 Herlev, Denmark. [Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, FI-00029 Helsinki, Hus, Finland. [Aittomaki, Kristiina; Blomqvist, Carl] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Hus, Finland. [Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, FI-00029 Helsinki, Hus, Finland. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, FI-00029 Helsinki, Hus, Finland. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Olson, Janet E.; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [John, Esther M.; West, Dee W.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [John, Esther M.; Whittemore, Alice S.; West, Dee W.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 11001000, DC, Colombia. [Ulmer, Hans Ulrich] Frauenklin Stadtklin Baden Baden, D-76532 Baden Baden, Germany. [Rudiger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZC Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 ZC Leiden, Netherlands. [Seynaeve, Caroline] Erasmus MC Daniel den Hoed Canc Ctr, Family Canc Clin, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. [Van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2333 ZC Leiden, Netherlands. [Eccles, Diana M.; Tapper, William J.; Durcan, Lorraine] Univ Southampton, Fac Med, Southampton SO17 1BJ, Hants, England. [Jones, Louise] Queen Mary Univ London, London E1 4NS, England. [Peto, Julian; dos-Santos-Silva, Isabel] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England. [Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Dwek, Miriam; Swann, Ruth] Univ Westminster, Fac Sci & Technol, Dept Mol & Appl Biosci, London W1W 6UW, England. [Bane, Anita L.] Juravinski Hosp, Dept Pathol & Mol Med, Hamilton, ON L8V 1C3, Canada. [Bane, Anita L.] McMaster Univ, Ctr Canc, Hamilton, ON L8V 1C4, Canada. [Glendon, Gord] Mt Sinai Hosp, Ontario Canc Genet Network, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna M.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Mulligan, Anna M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Giles, Graham G.; Milne, Roger L.; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Giles, Graham G.; Milne, Roger L.; Baglietto, Laura] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia. [McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic 3004, Australia. [Carpenter, Jane] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW 2145, Australia. [Clarke, Christine] Univ Sydney, Westmead Inst Canc Res, Sydney, NSW 2145, Australia. [Scott, Rodney] Univ Newcastle, Discipline Med Genet, Sch Biomed Sci & Pharm, Fac Hlth, Callaghan, NSW 2305, Australia. [Scott, Rodney] John Hunter Hosp, Div Genet, Hunter Area Pathol Serv, Newcastle, NSW 2305, Australia. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Bruning, Thomas] German Social Accident Insurance IPA, Inst Prevent & Occupat Med, D-44789 Bochum, Germany. [Ko, Yon-Dschun] Evangelische Kliniken Bonn gGmbH, D-53113 Bonn, Germany. [Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, CRUK YCR Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England. [Dork, Thilo] Hannover Med Sch, Clin Radiat Oncol, D-30625 Hannover, Germany. [Bogdanova, Natalia; Park-Simon, Tjoung-Won; Hillemanns, Peter] Hannover Med Sch, Dept Obstet & Gynaecol, D-30625 Hannover, Germany. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Epidemiol Program, Honolulu, HI 96813 USA. [Burwinkel, Barbara; Marme, Frederik; Surovy, Harald; Yang, Rongxi] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany. [Burwinkel, Barbara; Surovy, Harald; Yang, Rongxi] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany. [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Hooning, Maartje J.; Martens, John W. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Family Canc Clin, NL-3008 AE Rotterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, NL-3000 CA Rotterdam, Netherlands. [Tilanus-Linthorst, Madeleine M. A.] Erasmus Univ, Med Ctr, Dept Surg Oncol, Rotterdam, Netherlands. [Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volke] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, D-66119 Saarbrucken, Germany. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, NordLab Oulu Oulu Univ Hosp, Dept Clin Chem, Lab Canc Genet & Tumor Biol, FI-90220 Oulu, Finland. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, NordLab Oulu Oulu Univ Hosp, Bioctr Oulu, FI-90220 Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, FI-90220 Oulu, Finland. [Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, FI-90220 Oulu, Finland. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol & Pathol, SE-17177 Stockholm, Sweden. [Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr CNIO, Human Genotyping CEGEN Unit, Human Canc Genet Program, Madrid 28029, Spain. [Arias, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Asturias, Spain. [Zamora, Pilar] Hosp Univ La Paz, Serv Oncol Med, Madrid 28046, Spain. [Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, Kuopio 70210, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Canc Ctr, Kuopio 70210, Finland. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Teo, Soo H.] Sime Darby Med Ctr, Canc Res Initiat Fdn, Selangor, Malaysia. [Teo, Soo H.] Univ Malaya, Canc Res Inst, Fac Med, Kuala Lumpur 50603, Malaysia. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84108 USA. [Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84108 USA. [Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. RP Spurdle, AB (reprint author), QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. EM Amanda.Spurdle@qimrberghofer.edu.au RI Brinton, Louise/G-7486-2015; Spurdle, Amanda/A-4978-2011; montagna, marco/E-2225-2012; Hartikainen, Jaana/E-6256-2015; Teo, Soo-hwang/H-2353-2014; Bruning, Thomas/G-8120-2015; Dork, Thilo/J-8620-2012; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; OI Barrowdale, Daniel/0000-0003-1661-3939; Cross, Simon/0000-0003-2044-1754; Papi, Laura/0000-0003-4552-9517; Dunning, Alison Margaret/0000-0001-6651-7166; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Evans, Gareth/0000-0002-8482-5784; Brinton, Louise/0000-0003-3853-8562; Devilee, Peter/0000-0002-8023-2009; Spurdle, Amanda/0000-0003-1337-7897; montagna, marco/0000-0002-4929-2150; Bruning, Thomas/0000-0001-9560-5464; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Eeles, Rosalind/0000-0002-3698-6241 FU NHMRC Senior Research Fellowship; Australian NHMRC Project [1010719]; NIH [CA128978, CA116167]; NIH specialized program of research excellence in breast cancer to the Mayo Clinic [P50 CA116201]; Breast Cancer Research Foundation; Cancer Research-UK [C12292/A11174, C1287/A10118, C1287/A12014]; European Communitys Seventh Framework Programme [223175 HEALTH-F2-2009-223175] FX Amanda Spurdle is supported by an NHMRC Senior Research Fellowship, and aspects of this research were funded by Australian NHMRC Project grant ID 1010719. This work was supported in part by NIH grants CA128978 and CA116167, an NIH specialized program of research excellence in breast cancer to the Mayo Clinic (P50 CA116201), and the Breast Cancer Research Foundation. CIMBA data management was supported by Cancer Research-UK grant C12292/A11174 and C1287/A10118. ACA is a Cancer Research-UK Senior Cancer Research Fellow. BCAC data management was funded by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the European Communitys Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175). NR 54 TC 13 Z9 13 U1 4 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 6 AR 3419 DI 10.1186/s13058-014-0474-y PG 16 WC Oncology SC Oncology GA CB8NB UT WOS:000349885800041 PM 25857409 ER PT B AU Barh, D Carpi, A Verma, M Gunduz, M AF Barh, Debmalya Carpi, Angelo Verma, Mukesh Gunduz, Mehmet BE Barh, D Carpi, A Verma, M Gunduz, M TI Cancer Biomarkers Minimal and Noninvasive Early Diagnosis and Prognosis Preface SO CANCER BIOMARKERS: MINIMAL AND NONINVASIVE EARLY DIAGNOSIS AND PROGNOSIS LA English DT Editorial Material; Book Chapter C1 [Barh, Debmalya] Inst Integrat Omics & Appl Biotechnol, Ctr Genom & Appl Gene Technol, Nonakuri, India. [Carpi, Angelo] Univ Pisa, Dept Clin & Expt Med, Pisa, Italy. [Verma, Mukesh] NCI, NIH, Rockville, MD USA. [Gunduz, Mehmet] Turgut Ozal Univ, Dept Med Genet, Fac Med, Ankara, Turkey. RP Barh, D (reprint author), Inst Integrat Omics & Appl Biotechnol, Ctr Genom & Appl Gene Technol, Nonakuri, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8429-7; 978-1-4665-8428-0 PY 2014 BP XIII EP XIV D2 10.1201/b16389 PG 2 WC Plant Sciences; Medicine, Research & Experimental SC Plant Sciences; Research & Experimental Medicine GA BD5YZ UT WOS:000361916200002 ER PT B AU Verma, M Agarwal, N Verma, M AF Verma, Mukesh Agarwal, Neelesh Verma, Mudit BE Barh, D Carpi, A Verma, M Gunduz, M TI Mitochondrial DNA in Early Cancer Diagnosis and Screening SO CANCER BIOMARKERS: MINIMAL AND NONINVASIVE EARLY DIAGNOSIS AND PROGNOSIS LA English DT Article; Book Chapter DE cancer; detection; diagnosis; epidemiology; haplogroups; mitochondria; prognosis; risk assessment; screening; survival; treatment ID D-LOOP MUTATIONS; HUMAN HEPATOCELLULAR-CARCINOMA; HUMAN ENDOMETRIAL CARCINOMAS; CIRCULATING NUCLEIC-ACIDS; RENAL-CELL CARCINOMAS; SOMATIC MUTATIONS; BREAST-CANCER; PROSTATE-CANCER; COPY NUMBER; BLADDER-CANCER AB Biomarkers are used in cancer detection, diagnosis, and prognosis. In cancer, most genetic markers are based on nuclear DNA; mitochondrial DNA (mtDNA) has not been utilized very extensively. This article provides information about using mtDNA alterations as biomarkers to detect different tumor types at early stages of carcinogenesis. Mitochondria play an important role in cellular energy metabolism, free radical generation, and apoptosis. Alterations in respiratory activity and mtDNA alterations are an integral part of carcinogenesis. Mitochondria contain their own genome along with their own transcription, translation, and protein assembly machinery. Because mtDNA lacks introns, it does not have histones and is more susceptible to oxidative damage and other environmental insults. It has been suggested that most mutations and deletions will occur in coding sequences, and the subsequent accumulation of mutations may lead to tumor formation. Mitochondrial mutations have been reported in bladder, brain, breast, colon, cervical, esophageal, gastric, liver, lung, and prostate cancers. Some of these mutations occur quite early during cancer development and can be used in screening large populations to identify high-risk individuals. Mitochondrial DNA alteration can be detected in biospecimens collected non-invasively. The implications of using mitochondrial information in identifying populations that are at high risk of developing cancer are discussed. C1 [Verma, Mukesh; Agarwal, Neelesh; Verma, Mudit] NCI, NIH, Rockville, MD 20852 USA. RP Verma, M (reprint author), NCI, NIH, Rockville, MD 20852 USA. NR 133 TC 0 Z9 0 U1 1 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8429-7; 978-1-4665-8428-0 PY 2014 BP 95 EP 114 D2 10.1201/b16389 PG 20 WC Plant Sciences; Medicine, Research & Experimental SC Plant Sciences; Research & Experimental Medicine GA BD5YZ UT WOS:000361916200008 ER PT B AU Verma, M Barh, D Jain, N AF Verma, Mukesh Barh, Debmalya Jain, Neha BE Barh, D Carpi, A Verma, M Gunduz, M TI Noninvasive Early Markers in Lung Cancer SO CANCER BIOMARKERS: MINIMAL AND NONINVASIVE EARLY DIAGNOSIS AND PROGNOSIS LA English DT Article; Book Chapter DE biomarker; cancer; chromatin; diagnosis; early detection; epigenetics; genomic instability; histone; methylation; microRNA; prognosis; proteomics; surveillance; validation ID GENE PROMOTER METHYLATION; MALIGNANT-PLEURAL-MESOTHELIOMA; RISK-ASSESSMENT; PLASMA-LEVELS; MOLECULAR MARKERS; DNA METHYLATION; EPIGENETIC BIOMARKERS; CLINICAL-PRACTICE; MICRORNA MARKERS; TUMOR-MARKERS AB Lung cancer early markers are needed to develop strategies for prevention and treatment. A number of genetic, epigenetic, proteomic, metabolomic, and imaging biomarkers have been identified for lung cancer. Among proteomic biomarkers, GSTP1, HSPB1, and CKB showed promise because their levels increased with the progression of the disease, and these markers could be measured quantitatively with minimum amount of samples. Among epigenomic biomarkers, PAX5alpha, GATA5, and SULF2 methylation exhibited promise in lung cancer early diagnosis when sputum samples were analyzed. A systematic evaluation of biomarkers, their strengths and weaknesses, and potential use in early detection of lung cancer is discussed in this chapter. The importance of analytical and clinical validation of biomarkers and the challenges and opportunities in this field is also discussed. The emphasis is on minimally invasive biomarkers, which could be detected easily in biological fluids and can be used for screening and early diagnostics of lung cancer, before clinical manifestation. C1 [Verma, Mukesh] NCI, NIH, Rockville, MD 20852 USA. [Barh, Debmalya] Inst Integrat Omics & Appl Biotechnol, Ctr Genom & Appl Gene Technol, Nonakuri, India. [Jain, Neha] Inst Integrat Omics & Appl Biotechnol, Purba Medinipur, India. RP Verma, M (reprint author), NCI, NIH, Rockville, MD 20852 USA. NR 109 TC 0 Z9 0 U1 2 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8429-7; 978-1-4665-8428-0 PY 2014 BP 415 EP 431 D2 10.1201/b16389 PG 17 WC Plant Sciences; Medicine, Research & Experimental SC Plant Sciences; Research & Experimental Medicine GA BD5YZ UT WOS:000361916200020 ER PT B AU Basseville, A Robey, RW Bahr, JC Bates, SE AF Basseville, Agnes Robey, Robert W. Bahr, Julian C. Bates, Susan E. BE You, G Morris, ME TI BREAST CANCER RESISTANCE PROTEIN (BCRP) OR ABCG2 SO DRUG TRANSPORTERS: MOLECULAR CHARACTERIZATION AND ROLE IN DRUG DISPOSITION, 2ND EDITION SE Wiley Series in Drug Discovery and Development LA English DT Article; Book Chapter ID ACUTE-MYELOID-LEUKEMIA; BINDING CASSETTE TRANSPORTER; SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL LUNG-CANCER; URIC-ACID LEVELS; GENOME-WIDE ASSOCIATION; N-LINKED GLYCOSYLATION; P-GLYCOPROTEIN ABCB1; MEDIATED PROTEASOMAL DEGRADATION C1 [Basseville, Agnes; Robey, Robert W.; Bahr, Julian C.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Basseville, A (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 308 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-70530-8; 978-1-118-48993-2 J9 WILEY SER DRUG DISC PY 2014 BP 187 EP 221 D2 10.1002/9781118705308 PG 35 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD6BR UT WOS:000362007500013 ER PT B AU Nath, A Li, WX AF Nath, Avindra Li, Wenxue BE Joska, JA Stein, DJ Grant, I TI Host Genetics in HIV-Associated Neurocognitive Disorders SO HIV AND PSYCHIATRY SE Current Science and Clinical Practice Series LA English DT Editorial Material; Book Chapter ID DISEASE PROGRESSION; APOLIPOPROTEIN-E; COGNITIVE IMPAIRMENT; AIDS DEMENTIA; GENOTYPE; ALLELE; APOE; RISK; INFECTION; CHILDREN C1 [Nath, Avindra; Li, Wenxue] NINDS, NIH, Bethesda, MD 20892 USA. RP Nath, A (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-33954-1; 978-1-118-33953-4 J9 CURR SCI CLIN PRACT PY 2014 BP 93 EP 98 D2 10.1002/9781118339503 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD6FG UT WOS:000362174700010 ER PT B AU Zakharov, A Lagunin, A AF Zakharov, Alexey Lagunin, Alexey BE Gorb, L Kuzmin, V Muratov, E TI Computational Toxicology in Drug Discovery: Opportunities and Limitations SO APPLICATION OF COMPUTATIONAL TECHNIQUES IN PHARMACY AND MEDICINE SE Challenges and Advances in Computational Chemistry and Physics LA English DT Article; Book Chapter ID CHEMICAL-STRUCTURE; MARKETED PHARMACEUTICALS; RODENT CARCINOGENICITY; PREDICTIVE TOXICOLOGY; ACUTE TOXICITY; DATA QUALITY; P450 ENZYME; QSAR MODELS; DATABASE; TARGETS AB Different methods of computational toxicology are used in drug discovery to reveal toxic and dangerous side effects of drug candidates on early stages of drug development. Information about chemoinformatic, toxicogenomic and system biological approaches, commercial and freely available software and resources with data about toxicity of chemicals used in computational toxicology are represented. General rules and key components of QSAR modeling in respect to opportunities and limitations of computational toxicology in drug discovery are considered. The questions of computer evaluation of drug interaction with antitargets, drug-metabolizing enzymes, drug-transporters and related with such interaction toxic and side effects are discussed in the chapter. Along with an overview of existing approaches we give examples of the practical application of computer programs GUSAR, PASS and PharmaExpert to assess the general toxicity and toxic properties of individual drug-like compounds and drug combinations. C1 [Zakharov, Alexey] NCI, NIH, Biol Chem Lab, Frederick, MD 21702 USA. [Lagunin, Alexey] Russian Acad Med Sci, Orechovich Inst Biomed Chem, Lab Struct Funct Based Drug Design, Moscow 119121, Russia. RP Zakharov, A (reprint author), NCI, NIH, Biol Chem Lab, 376 Boyles St, Frederick, MD 21702 USA. EM alexey.zakharov@nih.gov; alexey.lagunin@ibmc.msk.ru RI Lagunin, Alexey/G-3745-2010 OI Lagunin, Alexey/0000-0003-1757-8004 NR 86 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-94-017-9257-8; 978-94-017-9256-1 J9 CHALL ADV COMPUT CHE PY 2014 VL 17 BP 325 EP 367 DI 10.1007/978-94-017-9257-8_11 D2 10.1007/978-94-017-9257-8 PG 43 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD2DB UT WOS:000358669000012 ER PT S AU Bilgel, M Carass, A Resnick, SM Wong, DF Prince, JL AF Bilgel, Murat Carass, Aaron Resnick, Susan M. Wong, Dean F. Prince, Jerry L. BE Wu, G Zhang, D Zhou, L TI Deformation Field Correction for Spatial Normalization of PET Images Using a Population-Derived Partial Least Squares Model SO MACHINE LEARNING IN MEDICAL IMAGING (MLMI 2014) SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Machine Learning in Medical Imaging (MLMI) CY SEP 14, 2014 CL Massachusetts Inst Technol, Cambridge, MA HO Massachusetts Inst Technol DE PET registration; deformation field; partial least squares ID ALZHEIMER-DISEASE PATIENTS; REGISTRATION AB Spatial normalization of positron emission tomography (PET) images is essential for population studies, yet work on anatomically accurate PET-to-PET registration is limited. We present a method for the spatial normalization of PET images that improves their anatomical alignment based on a deformation correction model learned from structural image registration. To generate the model, we first create a population-based PET template with a corresponding structural image template. We register each PET image onto the PET template using deformable registration that consists of an affine step followed by a diffeomorphic mapping. Constraining the affine step to be the same as that obtained from the PET registration, we find the diffeomorphic mapping that will align the structural image with the structural template. We train partial least squares (PLS) regression models within small neighborhoods to relate the PET intensities and deformation fields obtained from the diffeomorphic mapping to the structural image deformation fields. The trained model can then be used to obtain more accurate registration of PET images to the PET template without the use of a structural image. A cross validation based evaluation on 79 subjects shows that our method yields more accurate alignment of the PET images compared to deformable PET-to-PET registration as revealed by 1) a visual examination of the deformed images, 2) a smaller error in the deformation fields, and 3) a greater overlap of the deformed anatomical labels with ground truth segmentations. C1 [Bilgel, Murat; Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD 21218 USA. [Bilgel, Murat; Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Wong, Dean F.; Prince, Jerry L.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP Bilgel, M (reprint author), Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD 21218 USA. OI Carass, Aaron/0000-0003-4939-5085 NR 11 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-10581-9; 978-3-319-10580-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8679 BP 198 EP 206 PG 9 WC Computer Science, Artificial Intelligence; Medical Informatics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BD3US UT WOS:000360206000025 ER PT S AU Santosh, KC Wendling, L Antani, SK Thoma, GR AF Santosh, K. C. Wendling, Laurent Antani, Sameer K. Thoma, George R. GP IEEE TI Scalable Arrow Detection in Biomedical Images SO 2014 22ND INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION (ICPR) SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 22nd International Conference on Pattern Recognition (ICPR) CY AUG 24-28, 2014 CL Swedish Soc Automated Image Anal, Stockholm, SWEDEN SP IEEE Comp Soc, IAPR, Linkopings Univ, Lunds Univ, Uppsala Univ, e Sci Collaborat, Swedish Soc Automated Image Anal, Stockhoms Stad, Swedish e Sci Res Ctr, SICK, Autoliv, IBM Res, Int Journal Automat & Comp HO Swedish Soc Automated Image Anal DE Arrow detection; biomedical images; content-based image retrieval and text information retrieval ID PERFORMANCE; ALGORITHM AB In this paper, we present a scalable arrow detection technique for biomedical images to support information retrieval systems under the purview of content-based image retrieval (CBIR) and text information retrieval (TIR). The idea primarily follows the criteria based on the geometric properties of the arrow, where we introduce signatures from key points associated with it. To handle this, images are first binarized via a fuzzy binarization tool and several regions of interest are labeled accordingly. Each region is used to generate signatures and then compared with the theoretical ones to check their similarity. Our validation over biomedical images shows the advantage of the technique over the most prominent state-of-the-art methods. C1 [Santosh, K. C.; Antani, Sameer K.; Thoma, George R.] NIH, Commun Engn Branch, US Natl Lib Med NLM, Bethesda, MD 20894 USA. [Wendling, Laurent] Univ Paris 05, SIP LIPADE, F-75270 Paris 06, France. RP Santosh, KC (reprint author), NIH, Commun Engn Branch, US Natl Lib Med NLM, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM Santosh.KC@nih.gov; Laurent.Wendling@parisdescartes.fr; Sameer.Antani@nih.gov; George.Thoma@nih.gov NR 16 TC 2 Z9 2 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1051-4651 BN 978-1-4799-5208-3 J9 INT C PATT RECOG PY 2014 BP 3257 EP 3262 DI 10.1109/ICPR.2014.561 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BD3KX UT WOS:000359818003065 ER PT J AU Lovinger, DM Zhou, Z Heilig, M Goldman, D AF Lovinger, D. M. Zhou, Z. Heilig, M. Goldman, D. TI Mechanisms Underlying the mGluR2 Autoreceptor Function and Its Role in Control of Alcohol Drinking SO CURRENT NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 [Lovinger, D. M.; Zhou, Z.; Heilig, M.; Goldman, D.] NIAAA, NIH, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2014 VL 12 SU 1 MA 97 BP 37 EP 37 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CP5SJ UT WOS:000359944100098 ER PT J AU Nisenbaum, ES Iyengar, S Knopp, KL Simmons, RMA Li, DL Fisher, MJ Kuklish, S Barth, VN Chambers, MG Heinz, BA Monk, SA Zanotti-Fregonara, P Liow, JS Xu, R Pike, VW Innis, RB Arendt-Nielsen, LA AF Nisenbaum, E. S. Iyengar, S. Knopp, K. L. Simmons, R. M. A. Li, D. L. Fisher, M. J. Kuklish, S. Barth, V. N. Chambers, M. G. Heinz, B. A. Monk, S. A. Zanotti-Fregonara, P. Liow, J. -S. Xu, R. Pike, V. W. Innis, R. B. Arendt-Nielsen, L. A. TI LY2491503, a Novel mGluR1 Antagonist for Persistent Pain: from Clone to Clinic SO CURRENT NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 [Arendt-Nielsen, L. A.] C4Pain, Aalborg, Denmark. [Nisenbaum, E. S.; Iyengar, S.; Knopp, K. L.; Simmons, R. M. A.; Li, D. L.; Fisher, M. J.; Kuklish, S.; Barth, V. N.; Chambers, M. G.; Heinz, B. A.; Monk, S. A.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Nisenbaum, E. S.; Iyengar, S.; Knopp, K. L.; Simmons, R. M. A.; Li, D. L.; Fisher, M. J.; Kuklish, S.; Barth, V. N.; Chambers, M. G.; Heinz, B. A.; Monk, S. A.] NIMH, Bethesda, MD 20892 USA. EM nisenbaum_eric_s@lilly.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2014 VL 12 SU 1 MA 122 BP 47 EP 48 PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CP5SJ UT WOS:000359944100123 ER PT J AU Samadi, M Dudek, SM Bashir, ZI AF Samadi, M. Dudek, S. M. Bashir, Z. I. TI Group I mGluR-Dependent Plasticity in Hippocampal CA2 SO CURRENT NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 [Samadi, M.; Bashir, Z. I.] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England. [Dudek, S. M.] NIEHS, Synapt & Dev Plast Unit, Res Triangle Pk, NC 27709 USA. EM m.samadi@bristol.ac.uk NR 5 TC 0 Z9 0 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2014 VL 12 SU 1 MA 140 BP 54 EP 54 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CP5SJ UT WOS:000359944100141 ER PT S AU Kastrin, A Rindflesch, TC Hristovski, D AF Kastrin, Andrej Rindflesch, Thomas C. Hristovski, Dimitar BE Dzeroski, S Panov, P Kocev, D Todorovski, L TI Link Prediction on the Semantic MEDLINE Network An Approach to Literature-Based Discovery SO DISCOVERY SCIENCE, DS 2014 SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT 17th International Conference on Discovery Science (DS) CY OCT 08-10, 2014 CL Bled, SLOVENIA SP Jozef Stefan Inst, Dept Knowledge Technologies, Univ Ljubljana DE Literature-based discovery; Network analysis; Link prediction; Semantic network ID COMPLEX NETWORKS; BIOMEDICAL TEXT; KNOWLEDGE AB Retrieving and linking different segments of scientific information into understandable and interpretable knowledge is a challenging task. Literature-based discovery (LBD) is a methodology for automatically generating hypotheses for scientific research by uncovering hidden, previously unknown relationships from existing knowledge (published literature). Semantic MEDLINE is a database consisting of semantic predications extracted from MEDLINE citations. The predications provide a normalized form of the meaning of the text. The associations between the concepts in these predications can be described in terms of a network, consisting of nodes and directed arcs, where the nodes represent biomedical concepts and the arcs represent their semantic relationships. In this paper we propose and evaluate a methodology for link prediction of implicit relationships in the Semantic MEDLINE network. Link prediction was performed using different similarity measures including common neighbors, Jaccard index, and preferential attachment. The proposed approach is complementary to, and may augment, existing LBD approaches. The analyzed network consisted of 231,589 nodes and 10,061,747 directed arcs. The results showed high prediction performance, with the common neighbors method providing the best area under the ROC curve of 0.96. C1 [Kastrin, Andrej] Fac Informat Studies, Novo Mesto, Slovenia. [Rindflesch, Thomas C.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Ljubljana, Slovenia. RP Kastrin, A (reprint author), Fac Informat Studies, Novo Mesto, Slovenia. EM andrej.kastrin@guest.arnes.si; trindflesch@mail.nih.gov; dimitar.hristovski@mf.uni-lj.si NR 19 TC 3 Z9 3 U1 2 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-11812-3; 978-3-319-11811-6 J9 LECT NOTES ARTIF INT PY 2014 VL 8777 BP 135 EP 143 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Robotics SC Computer Science; Robotics GA BD3TZ UT WOS:000360154800012 ER PT J AU Roberts, K Masterton, K Fiszman, M Kilicoglu, H Demner-Fushman, D AF Roberts, Kirk Masterton, Kate Fiszman, Marcelo Kilicoglu, Halil Demner-Fushman, Dina BE Calzolari, N Choukri, K Declerck, T Loftsson, H Maegaard, B Mariani, J Moreno, A Odijk, J Piperidis, S TI Annotating Question Decomposition on Complex Medical Questions SO LREC 2014 - NINTH INTERNATIONAL CONFERENCE ON LANGUAGE RESOURCES AND EVALUATION LA English DT Proceedings Paper CT 9th International Conference on Language Resources and Evaluation (LREC) CY MAY 26-31, 2014 CL Reykjavik, ICELAND SP Holmes Semant Solut, European Media Lab GmBH, EML, VoiceBox Technologies, KDICTIONARIES DE question decomposition; question answering; medical language processing ID CLINICAL QUESTIONS; SYSTEM AB This paper presents a method for annotating question decomposition on complex medical questions. The annotations cover multiple syntactic ways that questions can be decomposed, including separating independent clauses as well as recognizing coordinations and exemplifications. We annotate a corpus of 1,467 multi-sentence consumer health questions about genetic and rare diseases. Furthermore, we label two additional medical-specific annotations: (1) background sentences are annotated with a number of medical categories such as symptoms, treatments, and family history, and (2) the central focus of the complex question (a disease) is marked. We present simple baseline results for automatic classification of these annotations, demonstrating the challenging but important nature of this task. C1 [Roberts, Kirk; Masterton, Kate; Fiszman, Marcelo; Kilicoglu, Halil; Demner-Fushman, Dina] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Roberts, K (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM kirk.roberts@nih.gov; ddemner@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN LANGUAGE RESOURCES ASSOC-ELRA PI PARIS PA 55-57, RUE BRILLAT-SAVARIN, PARIS, 75013, FRANCE BN 978-2-9517408-8-4 PY 2014 BP 2598 EP 2602 PG 5 WC Linguistics; Language & Linguistics SC Linguistics GA BC8FH UT WOS:000355611004035 ER PT J AU Dogan, RI Wilbur, WJ Comeau, DC AF Dogan, Rezarta Islamaj Wilbur, W. John Comeau, Donald C. BE Calzolari, N Choukri, K Declerck, T Loftsson, H Maegaard, B Mariani, J Moreno, A Odijk, J Piperidis, S TI BioC and Simplified Use of the PMC Open Access Dataset for Biomedical Text Mining SO LREC 2014 - NINTH INTERNATIONAL CONFERENCE ON LANGUAGE RESOURCES AND EVALUATION LA English DT Proceedings Paper CT 9th International Conference on Language Resources and Evaluation (LREC) CY MAY 26-31, 2014 CL Reykjavik, ICELAND SP Holmes Semant Solut, European Media Lab GmBH, EML, VoiceBox Technologies, KDICTIONARIES DE interoperability; PubMed Central; biomedical natural language processing; BioC; annotations ID INFORMATION EXTRACTION; BIOLOGICAL LITERATURE; FULL-TEXT; DEFINITIONS; SEARCH AB High quality easily-accessible resources are crucial for developing reliable applications in the health and biomedical domain. At the same time, interoperability, broad use, and reuse are vital considerations when developing useful systems. As a response, BioC has recently been put forward as a convenient XML format to share text documents and annotations, and as an accompanying input/output library to promote interoperability of data and tools. The BioC approach allows a large number of different textual annotations to be represented, and permits developers to more easily and efficiently share training data, supportive software modules and produced results. Here we give a brief overview of BioC resources. We also present the BioC-PMC dataset as a new resource, which contains all the articles available from the PubMed Central Open Access collection conveniently packaged in the BioC format. We show how this valuable resource can be easily used for text-mining tasks. Code and data are available for download at the BioC site: http://bioc.sourceforge.net. C1 [Dogan, Rezarta Islamaj; Wilbur, W. John; Comeau, Donald C.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Dogan, RI (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM Rezarta.Islamaj@nih.gov; wilbur@ncbi.nlm.nih.gov; comeau@ncbi.nlm.nih.gov NR 29 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN LANGUAGE RESOURCES ASSOC-ELRA PI PARIS PA 55-57, RUE BRILLAT-SAVARIN, PARIS, 75013, FRANCE BN 978-2-9517408-8-4 PY 2014 PG 8 WC Linguistics; Language & Linguistics SC Linguistics GA BC8FH UT WOS:000355611000008 ER PT J AU Roberts, K Masterton, K Fiszman, M Kilicoglu, H Demner-Fushman, D AF Roberts, Kirk Masterton, Kate Fiszman, Marcelo Kilicoglu, Halil Demner-Fushman, Dina BE Calzolari, N Choukri, K Declerck, T Loftsson, H Maegaard, B Mariani, J Moreno, A Odijk, J Piperidis, S TI Annotating Question Types for Consumer Health Questions SO LREC 2014 - NINTH INTERNATIONAL CONFERENCE ON LANGUAGE RESOURCES AND EVALUATION LA English DT Proceedings Paper CT 9th International Conference on Language Resources and Evaluation (LREC) CY MAY 26-31, 2014 CL Reykjavik, ICELAND SP Holmes Semant Solut, European Media Lab GmBH, EML, VoiceBox Technologies, KDICTIONARIES DE question classification; question answering; medical language processing ID CLASSIFICATION AB This paper presents a question classification scheme and a corresponding annotated corpus of consumer health questions. While most medical question classification methods have targeted medical professionals, the 13 question types we present are targeted toward disease questions posed by consumers. The corpus consists of 1,467 consumer-generated requests for disease information, containing a total of 2,937 questions. The goal of question type classification is to indicate the best strategy for selecting answers from publicly available health information resources, such as medical encyclopedias and medical research websites. The annotated question corpus, along with detailed annotation guidelines, are publicly available. C1 [Roberts, Kirk; Masterton, Kate; Fiszman, Marcelo; Kilicoglu, Halil; Demner-Fushman, Dina] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Roberts, K (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM kirk.roberts@nih.gov; ddemner@mail.nih.gov NR 26 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN LANGUAGE RESOURCES ASSOC-ELRA PI PARIS PA 55-57, RUE BRILLAT-SAVARIN, PARIS, 75013, FRANCE BN 978-2-9517408-8-4 PY 2014 PG 8 WC Linguistics; Language & Linguistics SC Linguistics GA BC8FH UT WOS:000355611000009 ER PT B AU Albert, S Rossmann, JS Balaban, R AF Albert, Scott Rossmann, Jenn Stroud Balaban, Robert GP ASME TI NUMERICAL SIMULATION OF BLOOD FLOW IN THE RENAL ARTERIES: INFLUENCE OF THE OSTIUM FLOW DIVERTER SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2013, PT B LA English DT Proceedings Paper CT 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013) CY JUN 26-29, 2013 CL Sunriver, OR SP Amer Soc Mech Engn, Bioengineer Div C1 [Albert, Scott] Lafayette Coll, Chem & Biomol Engn, Easton, PA 18042 USA. [Rossmann, Jenn Stroud] Lafayette Coll, Mech Engn, Easton, PA 18042 USA. [Balaban, Robert] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Albert, S (reprint author), Lafayette Coll, Chem & Biomol Engn, Easton, PA 18042 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5561-4 PY 2014 AR V01BT58A002 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YI UT WOS:000359389300236 ER PT B AU Borchelt, RE Nielsen, KH AF Borchelt, Rick E. Nielsen, Kristian H. BE Bucchi, M Trench, B TI Public relations in science Managing the trust portfolio SO ROUTLEDGE HANDBOOK OF PUBLIC COMMUNICATION OF SCIENCE AND TECHNOLOGY, 2ND EDITION SE Routledge International Handbooks LA English DT Article; Book Chapter ID STRATEGIC RISK COMMUNICATION; E-MAIL; WEB; POLITICS C1 [Borchelt, Rick E.] US DOE, Commun & Publ Affairs, Off Sci, Washington, DC 20585 USA. [Borchelt, Rick E.] US Natl Canc Inst, Bethesda, MD USA. [Borchelt, Rick E.] USDA, Sci & Technol Publ Affairs, Washington, DC USA. [Borchelt, Rick E.] NASA, Washington, DC USA. [Borchelt, Rick E.] Univ Maryland, Bethesda, MD USA. [Borchelt, Rick E.] Johns Hopkins Univ, Genet & Publ Policy Ctr, Baltimore, MD 21218 USA. [Borchelt, Rick E.] Natl Acad Sci, Washington, DC USA. [Borchelt, Rick E.] Sci & Technol Publ Affairs Clinton Adm, New York, NY USA. [Borchelt, Rick E.] Vanderbilt Univ, Sci Commun & Sci Policy, Nashville, TN USA. [Borchelt, Rick E.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Nielsen, Kristian H.] Aarhus Univ, Ctr Sci Studies, Hist Sci & Sci Commun, DK-8000 Aarhus C, Denmark. RP Borchelt, RE (reprint author), US DOE, Commun & Publ Affairs, Off Sci, Washington, DC 20585 USA. NR 53 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-203-48379-4; 978-0-415-83461-2 J9 ROUT INT HANDB PY 2014 BP 58 EP 69 PG 12 WC Communication; Social Issues SC Communication; Social Issues GA BC9SB UT WOS:000356818300006 ER PT J AU Dixon, D Alison, R Bach, U Colman, K Foley, GL Harleman, JH Haworth, R Herbert, R Heuser, A Long, G Mirsky, M Regan, K Van Esch, E Westwood, FR Vidal, J Yoshida, M AF Dixon, Darlene Alison, Roger Bach, Ute Colman, Karyn Foley, George L. Harleman, Johannes H. Haworth, Richard Herbert, Ronald Heuser, Anke Long, Gerald Mirsky, Michael Regan, Karen Van Esch, Eric Westwood, F. Russell Vidal, Justin Yoshida, Midori TI Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System SO JOURNAL OF TOXICOLOGIC PATHOLOGY LA English DT Review DE diagnostic pathology; nomenclature; female reproductive; ovary; uterus; cervix; vagina ID GRANULAR-CELL TUMORS; SPRAGUE-DAWLEY RATS; ENDOMETRIAL ADENOCARCINOMA DEVELOPMENT; GLYCOL MONOMETHYL ETHER; OVARIAN TOXICITY; COLLABORATIVE WORK; B6C3F1 MICE; DONRYU RATS; 4-VINYLCYCLOHEXENE DIEPOXIDE; NEONATAL EXPOSURE AB The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (SIP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. (DOI: 10.1293/tox.27.1S: J Toxicol Pathol 2014; 27: 1S-107S C1 [Dixon, Darlene] NIEHS, NTP, Res Triangle Pk, NC 27709 USA. [Alison, Roger] Roger Alison Ltd, Pathol Consultancy Serv, Caerfyrddin Fach, Lampeter SA48 8RN, Dyfed, Wales. [Bach, Ute] Bayer Pharma AG, Wuppertal, Germany. [Colman, Karyn] Novartis, Novartis Inst Biomed Res, E Hanover, NJ USA. [Foley, George L.] AbbVie Inc, N Chicago, IL USA. [Harleman, Johannes H.] Fresenitis Kabi Deutschland GmbH, Bad Homburg, Germany. [Haworth, Richard] GlaxoSmithKline R&D, Ware SG12 0DP, Herts, England. [Herbert, Ronald] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Heuser, Anke] Roche Innovat Ctr Basel, Roche Phartna Res & Early Dev, CH-4070 Basel, Switzerland. [Long, Gerald] Expt Pathol Labs, Indianapolis, IN USA. [Mirsky, Michael] Pizer Worldwide Res & Dev, Groton, CT USA. [Regan, Karen] Regan Path Tox Serv, Ashland, OH USA. [Van Esch, Eric] InSight Pathol BV, Oss, Netherlands. [Westwood, F. Russell] AstraZeneca, Macclesfield, Cheshire, England. [Vidal, Justin] GlaxoSmithKline, King Of Prussia, PA USA. [Yoshida, Midori] Natl Inst Hlth Sci, Tokyo, Japan. RP Dixon, D (reprint author), NIEHS, NTP, POB 12233,MDB3-00-B341,3 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov NR 212 TC 18 Z9 18 U1 0 U2 1 PU JAPANESE SOC TOXICOLOGIC PATHOLOGY PI TOKYO PA DEPT ACAD SOC, MEDICAL TRIBUNE INC, ITALIAN CULTURAL INST BLDG 8F 2-1-30, KUDAN MINAMI, CHIYODA, TOKYO, 102-0074, JAPAN SN 0914-9198 EI 1881-915X J9 J TOXICOL PATHOL JI J. Toxicol. Pathol. PY 2014 VL 27 IS 3-4 SU S BP 1S EP 107S DI 10.1293/tox.27.1S PG 107 WC Pathology; Toxicology SC Pathology; Toxicology GA CN8PU UT WOS:000358703900001 PM 25516636 ER PT B AU Andrade, LF Petry, NM AF Andrade, Leonardo F. Petry, Nancy M. BE McSweeney, FK Murphy, ES TI Contingency Management Treatments for Substance-Use Disorders and Healthy Behaviors SO WILEY BLACKWELL HANDBOOK OF OPERANT AND CLASSICAL CONDITIONING LA English DT Article; Book Chapter ID VOUCHER-BASED REINFORCEMENT; DRUG-ABUSE TREATMENT; RESISTANT METHADONE PATIENTS; CARBON-MONOXIDE REDUCTION; CLINICAL-TRIALS NETWORK; COCAINE ABSTINENCE; RANDOMIZED-TRIAL; CIGARETTE-SMOKING; TREATMENT PROGRAM; WEIGHT-LOSS C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Storrs, CT USA. [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Med, Storrs, CT USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. [Petry, Nancy M.] Vet Adm, Morristown, NJ USA. RP Andrade, LF (reprint author), Univ Connecticut, Sch Med, Storrs, CT 06269 USA. NR 78 TC 2 Z9 2 U1 2 U2 2 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-46816-6; 978-1-118-46818-0 PY 2014 BP 627 EP 644 D2 10.1002/9781118468135 PG 18 WC Psychology, Clinical; Psychology, Applied SC Psychology GA BC9NC UT WOS:000356628400027 ER PT B AU Holbrook, K AF Holbrook, Karen BE Longman, KA Madsen, SR TI GROUNDED SO WOMEN AND LEADERSHIP IN HIGHER EDUCATION SE Women and Leadership LA English DT Article; Book Chapter C1 [Holbrook, Karen] Univ S Florida, Tampa, FL 33620 USA. [Holbrook, Karen] Univ S Florida, Res & Innovat, Tampa, FL 33620 USA. [Holbrook, Karen] Univ S Florida, Global Affairs & Int Res, Tampa, FL 33620 USA. [Holbrook, Karen] Ohio State Univ, Columbus, OH 43210 USA. [Holbrook, Karen] Univ Georgia, Athens, GA 30602 USA. [Holbrook, Karen] Univ Florida, Gainesville, FL 32611 USA. [Holbrook, Karen] Univ Washington, Sch Med UWSOM, Res, Seattle, WA 98195 USA. [Holbrook, Karen] Univ Washington, Sch Med UWSOM, Biol Struct & Med, Seattle, WA 98195 USA. [Holbrook, Karen] NIH, Bethesda, MD USA. RP Holbrook, K (reprint author), Univ S Florida, Tampa, FL 33620 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU INFORMATION AGE PUBLISHING-IAP PI CHARLOTTE PA PO BOX 79049, CHARLOTTE, NC 28271-7047 USA BN 978-1-62396-819-9; 978-1-62396-820-5 J9 WOMEN LEADERSH PY 2014 BP 219 EP 225 PG 7 WC Education & Educational Research; Management; Women's Studies SC Education & Educational Research; Business & Economics; Women's Studies GA BC9JH UT WOS:000356464600016 ER PT S AU Helmer, A Muller, F Lohmann, O Thiel, A Kretschmer, F Eichelberg, M Hein, A AF Helmer, Axel Mueller, Frerk Lohmann, Okko Thiel, Andreas Kretschmer, Friedrich Eichelberg, Marco Hein, Andreas BE FernandezChimeno, M Fernandes, PL Alvarez, S Stacey, D SoleCasals, J Fred, A Gamboa, H TI Integration of Smart Home Health Data in the Clinical Decision Making Process SO BIOMEDICAL ENGINEERING SYSTEMS AND TECHNOLOGIES (BIOSTEC 2013) SE Communications in Computer and Information Science LA English DT Proceedings Paper CT 6th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC) CY FEB 11-14, 2013 CL Barcelona, SPAIN SP Inst Syst & Technologies Informat Control & Commun, Univ Vic, Biomed Engn Soc, European Soc Engn & Med DE Telemedicine; Physiological modeling; Knowledge management; Electronic health records ID BEHAVIORAL-PATTERNS AB Patients suffering from COPD benefit from the performance of any kind of physical activity. The 3D layer context (3DLC) model characterizes data from smart home environments in relation to their relevance for the clinical decision making process. We have used this model to show how data from an ambient activity system in the domestic environment can be used to provide a more informed and thereby better treatment management for COPD patients. We set up an experiment to calculate an individual intensity relation between household activities and telerehabilitation training on a bicycle ergometer. We have extracted features from the power data of devices, which are used during the performance of two example every day activities to calculate the energy expenditure for the performance of these activities. C1 [Helmer, Axel; Mueller, Frerk; Lohmann, Okko; Thiel, Andreas; Eichelberg, Marco; Hein, Andreas] OFFIS Inst Informat Technol, R&D Div Hlth, D-26121 Oldenburg, Germany. [Kretschmer, Friedrich] NEI, NIH, NNRL, Bethesda, MD 20892 USA. RP Helmer, A (reprint author), OFFIS Inst Informat Technol, R&D Div Hlth, Escherweg 2, D-26121 Oldenburg, Germany. EM axel.helmer.job@gmail.com; frerk.mueller@offis.de; okko.lohmann@web.de; andreas.thiel@offis.de; frierich@kretschmer.de; marco.eichelberg@offis.de; andreas.hein@offis.de NR 24 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1865-0929 BN 978-3-662-44485-6; 978-3-662-44484-9 J9 COMM COM INF SC PY 2014 VL 452 BP 354 EP 366 DI 10.1007/978-3-662-44485-6_24 PG 13 WC Computer Science, Theory & Methods; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA BD1ZL UT WOS:000358524500024 ER PT B AU Plenz, D Niebur, E AF Plenz, Dietmar Niebur, Ernst BE Plenz, D Niebur, E TI Introduction SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth C1 [Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Niebur, Ernst] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Dept Neurosci, Baltimore, MD 21218 USA. RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 1 EP 3 PG 3 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300001 ER PT B AU Plenz, D AF Plenz, Dietmar BE Plenz, D Niebur, E TI Criticality in Cortex: Neuronal Avalanches and Coherence Potentials SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID SELF-ORGANIZED CRITICALITY; RANGE TEMPORAL CORRELATIONS; CAT CEREBRAL-CORTEX; CORTICAL ACTIVITY; PHASE-TRANSITIONS; SYNFIRE CHAINS; IN-VIVO; STRIATUM COCULTURES; SYNCHRONOUS SPIKING; STIMULUS PROPERTIES C1 NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. NR 150 TC 0 Z9 0 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 5 EP 42 PG 38 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300002 ER PT B AU Mandell, AJ Robinson, SE Selz, KA Schrader, C Holroyd, T Coppola, R AF Mandell, Arnold J. Robinson, Stephen E. Selz, Karen A. Schrader, Constance Holroyd, Tom Coppola, Richard BE Plenz, D Niebur, E TI The Turbulent Human Brain: An MHD Approach to the MEG SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID FAST-DYNAMO ACTION; CORTICAL ACTIVITY; MAGNETIC DYNAMOS; ERGODIC-THEORY; MAGNETOENCEPHALOGRAPHIC ANALYSIS; ALZHEIMERS-DISEASE; PYRAMIDAL NEURONS; METRIC INVARIANT; NEURAL NETWORKS; PHASE-LOCKING C1 [Mandell, Arnold J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Mandell, Arnold J.; Robinson, Stephen E.; Holroyd, Tom; Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA. [Mandell, Arnold J.; Robinson, Stephen E.; Selz, Karen A.] Fetzer Franklin Trust, Schoolcraft, MI 49087 USA. [Mandell, Arnold J.; Selz, Karen A.] Cielo Inst Inc, Asheville, NC 28804 USA. [Schrader, Constance] Univ N Carolina, Dept Hlth & Wellness, Asheville, NC 28804 USA. RP Mandell, AJ (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92037 USA. NR 145 TC 0 Z9 0 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 127 EP 151 PG 25 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300006 ER PT B AU Shriki, O Plenz, D AF Shriki, Oren Plenz, Dietmar BE Plenz, D Niebur, E TI Neuronal Avalanches in the Human Brain SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID RANGE TEMPORAL CORRELATIONS; CORTICAL NETWORKS; DYNAMICS; OSCILLATIONS; CRITICALITY C1 [Shriki, Oren; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. RP Shriki, O (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 177 EP 189 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300008 ER PT B AU Yu, S Yang, HD Shriki, O Plenz, D AF Yu, Shan Yang, Hongdian Shriki, Oren Plenz, Dietmar BE Plenz, D Niebur, E TI Critical Exponents, Universality Class, and Thermodynamic "Temperature'' of the Brain SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID HIGHER-ORDER INTERACTIONS; NEURONAL AVALANCHES; CORTICAL NETWORKS; DYNAMICS; ATTENTION; CORTEX; RANGE; EXCITABILITY; TRANSITIONS; PERFORMANCE C1 [Yu, Shan; Yang, Hongdian; Shriki, Oren; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Shriki, Oren] Ben Gurion Univ Negev, Dept Brain & Cognit Sci, IL-84105 Beer Sheva, Israel. RP Yu, S (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 319 EP 333 PG 15 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300014 ER PT B AU Yang, HD Shew, WL Roy, R Plenz, D AF Yang, Hongdian Shew, Woodrow L. Roy, Rajarshi Plenz, Dietmar BE Plenz, D Niebur, E TI Peak Variability and Optimal Performance in Cortical Networks at Criticality SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID VISUAL-CORTEX; NEURONAL AVALANCHES; RESPONSE VARIABILITY; INFORMATION CAPACITY; COMPLEX NETWORKS; NATURAL SCENES; IN-VIVO; BRAIN; FLUCTUATIONS; DISCHARGE C1 [Yang, Hongdian; Shew, Woodrow L.; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Shew, Woodrow L.] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA. [Shew, Woodrow L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Roy, Rajarshi] Univ Maryland, IPST, College Pk, MD 20742 USA. RP Yang, HD (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. NR 44 TC 1 Z9 1 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 335 EP 346 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300015 ER PT B AU Larremore, DB Shew, WL Restrepo, JG AF Larremore, Daniel B. Shew, Woodrow L. Restrepo, Juan G. BE Plenz, D Niebur, E TI Critical Dynamics in Complex Networks SO CRITICALITY IN NEURAL SYSTEMS LA English DT Proceedings Paper CT Conference on Criticality in Neural Systems CY APR 30-MAY 01, 2012 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID NEURONAL AVALANCHES; BRANCHING-PROCESSES; CORTICAL NETWORKS; OSCILLATIONS C1 [Larremore, Daniel B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Shew, Woodrow L.] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Restrepo, Juan G.] Univ Colorado, Dept Appl Math, Engn Ctr 526, Boulder, CO 80309 USA. RP Larremore, DB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65103-0; 978-3-527-41104-7 PY 2014 BP 365 EP 392 PG 28 WC Neurosciences SC Neurosciences & Neurology GA BD0UX UT WOS:000357734300017 ER PT B AU Nakyam, S AF Nakyam, Sukree BE Zhu, X Zhao, S TI Educational Decentralization Policy in Thailand: Unpacking Its Labyrinth to Pinpoint an Appropriately Further Step SO PROCEEDINGS OF 2014 INTERNATIONAL CONFERENCE ON PUBLIC ADMINISTRATION (10TH), VOL I LA English DT Proceedings Paper CT 10th International Conference on Public Administration CY OCT 24-26, 2014 CL Univ Elect Sci & Technol China, Sch Polit Sci & Publ Adm, Chengdu, PEOPLES R CHINA SP Univ Elect Sci & Technol China, Amer Soc Publ Adm, Chinese Publ Adm Soc, Chinese Publ Adm Journal, Moscow State Univ, Sch Publ Adm, Cape Peninsula Univ Technol, Fac Business, Univ Elect Sci & Technol China, PA Informat Res Ctr HO Univ Elect Sci & Technol China, Sch Polit Sci & Publ Adm DE Vertical and horizontal analysis; Narrative Policy Framework (NPF) ID CLIMATE-CHANGE; WORLD AB Thailand has introduced educational decentralization as one of public sector reforms for several forms over the last two decades. However, educational decentralization policy in Thailand indicates that it cannot satisfy its commonly expected goals. This article argues that educational decentralization policy faces a labyrinth of uniqueness resulting from the meet between travelling preferences and internally embedded factors. The article, therefore, provides an analysis of this policy over a wide range of dimensions in which vertical and horizontal perspectives are addressed to cover relevant factors. To serve this analysis, a policy analysis framework, the Narrative Policy Framework (NPF), is utilized. C1 NIDA, Bangkok 10310, Thailand. RP Nakyam, S (reprint author), NIDA, Bangkok 10310, Thailand. NR 34 TC 0 Z9 0 U1 1 U2 2 PU UNIV ELECTRONIC SCIENCE & TECHNOLOGY CHINA PRESS PI CHENGDU PA UESTC PRESS, CHENGDU, 610054, PEOPLES R CHINA BN 978-7-5647-2652-2 PY 2014 BP 655 EP 662 PG 8 WC Public Administration SC Public Administration GA BD0LX UT WOS:000357346100077 ER PT B AU Singhanat, R AF Singhanat, Rajbhandharak BE Zhu, X Zhao, S TI Collaborations in Crisis and Emergency Management :"One Mission Multiple Sectors (OMMS) Module" A Newly Designed Collaborative Mechanism for A Large Scale Disaster SO PROCEEDINGS OF 2014 INTERNATIONAL CONFERENCE ON PUBLIC ADMINISTRATION (10TH), VOL I LA English DT Proceedings Paper CT 10th International Conference on Public Administration CY OCT 24-26, 2014 CL Univ Elect Sci & Technol China, Sch Polit Sci & Publ Adm, Chengdu, PEOPLES R CHINA SP Univ Elect Sci & Technol China, Amer Soc Publ Adm, Chinese Publ Adm Soc, Chinese Publ Adm Journal, Moscow State Univ, Sch Publ Adm, Cape Peninsula Univ Technol, Fac Business, Univ Elect Sci & Technol China, PA Informat Res Ctr HO Univ Elect Sci & Technol China, Sch Polit Sci & Publ Adm DE Collaborations in Crisis and Emergency Management (CbCEM); Collaborative Mechanism; One Mission Multiple Sectors (OMMS) Module; Mutual Standard Operating Procedure (MSOP); Synchronized Emergency Management (SEM) AB This article addresses the comprehensive collaborative process, efforts and techniques essential for all relevant collaborative partners to work together in a single contingency strategic framework. When a large scale disaster happens, it seems to be "non-navigational" moment for all public private sectors due to their variety of management methodologies. The successful collaboration requires both the Art of Management and also Administrative Science. Central and local governments are to work together as well as the non-public organizations. Typical incident management structure, for instance Incident Command System (ICS) is too narrow in scope to be effective in the event of catastrophe or extremely large-scale disaster. There is no developed plan or pre-designed management structure for synchronized efforts among the public sector, private sector, and non-government organizations (NGO). In addition, establishing "One Mission Multiple Sectors (OMMS) Module" is an idea that has not yet been considered. This article views that well-prepared management structure can create partnership and successful collaborative network. Eventually, this typical collaborative mechanism may lead all relevant sectors to the effective escape way from labyrinth of management methodologies among them during the time of catastrophe. C1 NIDA, Bangkok 10310, Thailand. RP Singhanat, R (reprint author), NIDA, Bangkok 10310, Thailand. NR 8 TC 0 Z9 0 U1 0 U2 2 PU UNIV ELECTRONIC SCIENCE & TECHNOLOGY CHINA PRESS PI CHENGDU PA UESTC PRESS, CHENGDU, 610054, PEOPLES R CHINA BN 978-7-5647-2652-2 PY 2014 BP 999 EP 1004 PG 6 WC Public Administration SC Public Administration GA BD0LX UT WOS:000357346100124 ER PT B AU Baird, NJ West, J Sosnick, TR AF Baird, Nathan J. West, Jeremey Sosnick, Tobin R. BE Hartmann, RK Bindereif, A Schon, A Westhof, E TI RNA Structure and Folding Analyzed Using Small-Angle X-Ray Scattering SO HANDBOOK OF RNA BIOCHEMISTRY, VOLS 1 AND 2, 2ND EDITION LA English DT Article; Book Chapter ID BACTERIAL RIBONUCLEASE-P; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; RIBOSWITCH; RESOLUTION; RIBOZYME; TRANSITIONS; DIVERSITY; MODELS C1 [Baird, Nathan J.] NHLBI, NIH, Bethesda, MD 20892 USA. [West, Jeremey] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Sosnick, Tobin R.] Univ Chicago, Dept Biochem & Mol Biol, Inst Biophys Dynam, Chicago, IL 60637 USA. RP Baird, NJ (reprint author), NHLBI, NIH, 50 South Dr, Bethesda, MD 20892 USA. NR 32 TC 1 Z9 1 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-65055-2; 978-3-527-32764-5 PY 2014 BP 407 EP 425 D2 10.1002/9783527647064 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BD0PU UT WOS:000357533800021 ER PT B AU SanGiovanni, JP Neuringer, M AF SanGiovanni, John Paul Neuringer, Martha BE Landrum, JT Nolan, JM TI The Promise of Molecular Genetics for Investigating the Influence of Macular Xanthophyllys on Advanced Age-Related Macular Degeneration SO CAROTENOIDS AND RETINAL DISEASE LA English DT Article; Book Chapter ID PIGMENT OPTICAL-DENSITY; SJOGREN-LARSSON-SYNDROME; APOLIPOPROTEIN-E GENE; FATTY ALDEHYDE DEHYDROGENASE; BRONCHIAL EPITHELIAL-CELLS; S-TRANSFERASE M1; GROWTH IN-VITRO; HUMAN RETINA; BETA-CAROTENE; SCAVENGER RECEPTOR C1 [SanGiovanni, John Paul] NEI, Clin Trials Branch, Bethesda, MD 20892 USA. [Neuringer, Martha] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Portland, OR 97201 USA. RP SanGiovanni, JP (reprint author), NEI, Clin Trials Branch, Bethesda, MD 20892 USA. NR 150 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-0205-5; 978-1-4665-0204-8 PY 2014 BP 93 EP 128 PG 36 WC Ophthalmology SC Ophthalmology GA BC7TQ UT WOS:000355206800008 ER PT B AU Shih, JH AF Shih, Joanna H. BE Klein, JP VanHouwelingen, HC Ibrahim, JG Scheike, TH TI Copula Models SO HANDBOOK OF SURVIVAL ANALYSIS SE Chapman & Hall-CRC Handbooks of Modern Statistical Methods LA English DT Article; Book Chapter ID FAILURE-TIME DATA; OF-FIT TEST; SEMIPARAMETRIC ESTIMATION; ARCHIMEDEAN COPULAS; SURVIVAL MODELS; FRAILTY MODEL; DISTRIBUTIONS; ASSOCIATION; ESTIMATOR; PARAMETER C1 NCI, Bethesda, MD 20892 USA. RP Shih, JH (reprint author), NCI, Bethesda, MD 20892 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-5567-9; 978-1-4665-5566-2 J9 CH CRC HANDB MOD STA PY 2014 BP 489 EP 510 PG 22 WC Statistics & Probability SC Mathematics GA BC7MA UT WOS:000354996000030 ER PT J AU Pedrosa, GV Rahman, MM Antani, SK Demner-Fushman, D Long, LR Traina, AJM AF Pedrosa, Glauco V. Rahman, Md Mahmudur Antani, Sameer K. Demner-Fushman, Dina Long, L. Rodney Traina, Agma J. M. GP IEEE TI Integrating visual words as bunch of n-grams for effective biomedical image classification SO 2014 IEEE WINTER CONFERENCE ON APPLICATIONS OF COMPUTER VISION (WACV) LA English DT Proceedings Paper CT IEEE Winter Conference on Applications of Computer Vision (WACV) CY MAR 24-26, 2014 CL Steamboat Springs, CO SP IEEE AB The Bag-of-Visual-Words (BoVW) has been frequently used in the classification of image data. However, this modeling approach does not take into consideration the spatial relationships of these words, which is important for similarity measurement between images. We have developed a novel technique to incorporate spatial information of visual words based on the n-grams representation. The method encodes regional layout with a 2-gram representation in the local keypoint neighborhood. The region is divided in two zones to capture the relative orientations of pair-wise visual words. In turn, each image is described by an accumulated vector of 2-grams. Then, we compute the Shannon entropy over a random "bunch" of 2-grams to reduce the dimensionality of the feature vector. We discovered that this reduction technique creates a more discriminative feature vector as well as presents a considerable dimensionality reduction of up to 99%. The final representation is a compact and efficient local image descriptor that encodes frequency and arrangement of visual words. The proposed approach was tested by classifying a standard biomedical image dataset into categories defined by image modality and body part. The experimental results demonstrate the importance of contextual relations of visual words. Our proposed approach improved the classification accuracy compared to the traditional BoVW by 6.03%. C1 [Pedrosa, Glauco V.; Traina, Agma J. M.] Univ Sao Paulo, ICMC, Sao Carlos, SP, Brazil. [Rahman, Md Mahmudur; Antani, Sameer K.; Demner-Fushman, Dina; Long, L. Rodney] Natl Lib Med, NIH, Bethesda, MD USA. RP Pedrosa, GV (reprint author), Univ Sao Paulo, ICMC, Sao Carlos, SP, Brazil. EM gpedrosa@icmc.usp.br RI Traina, Agma/F-1299-2011; OI Traina, Agma/0000-0003-4929-7258; Antani, Sameer/0000-0002-0040-1387 NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA PY 2014 BP 431 EP 436 PG 6 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BC8WG UT WOS:000356144800060 ER PT B AU McCrae, RR Greenberg, DM AF McCrae, Robert R. Greenberg, David M. BE Simonton, DK TI Openness to Experience SO WILEY HANDBOOK OF GENIUS LA English DT Article; Book Chapter ID ADJECTIVE CHECK LIST; 5-FACTOR MODEL; PERSONALITY-TRAITS; SELF-REPORTS; CREATIVITY; UNIVERSAL; BIG-5; LIFE; AGE; INTELLIGENCE C1 [McCrae, Robert R.] NIA, Bethesda, MD 20892 USA. [Greenberg, David M.] Univ Cambridge, Cambridge CB2 1TN, England. NR 94 TC 5 Z9 5 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-36735-3; 978-1-118-36740-7 PY 2014 BP 222 EP 243 D2 10.1002/9781118367377 PG 22 WC Psychology, Multidisciplinary SC Psychology GA BC7FO UT WOS:000354810600013 ER PT B AU Varadan, VK Chen, LF Lee, J Mathur, GN Kim, HJ Choi, SH AF Varadan, Vijay K. Chen, Linfeng Lee, Jungmin Mathur, Gyanesh N. Kim, Hyun Jung Choi, Sang H. BE BarCohen, Y TI Thermoelectric Materials and Generators: Research and Application SO HIGH TEMPERATURE MATERIALS AND MECHANISMS LA English DT Article; Book Chapter ID BISMUTH TELLURIDE NANOPARTICLES; THERMAL-CONDUCTIVITY; TRANSPORT-PROPERTIES; SILICON NANOWIRES; POWER GENERATORS; GROWTH-MECHANISM; PHASE SYNTHESIS; HIGH FIGURE; THIN-FILMS; BODY HEAT C1 [Varadan, Vijay K.; Chen, Linfeng; Lee, Jungmin; Mathur, Gyanesh N.] Univ Arkansas, Dept Elect Engn, Fayetteville, AR 72701 USA. [Kim, Hyun Jung] NIA, Hampton, VA USA. [Choi, Sang H.] NASA Langley Res Ctr, Hampton, VA USA. RP Varadan, VK (reprint author), Univ Arkansas, Dept Elect Engn, Fayetteville, AR 72701 USA. NR 96 TC 0 Z9 0 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-6646-0; 978-1-4665-6645-3 PY 2014 BP 381 EP 426 D2 10.1201/b16545 PG 46 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA BC6BH UT WOS:000353719000014 ER PT B AU Schmidt, MW Ivanic, J Ruedenberg, K AF Schmidt, Michael W. Ivanic, Joseph Ruedenberg, Klaus BE Frenking, G Shaik, S TI The Physical Origin of Covalent Bonding SO CHEMICAL BOND: FUNDAMENTAL ASPECTS OF CHEMICAL BONDING LA English DT Article; Book Chapter ID MOLECULAR ELECTRONIC WAVEFUNCTIONS; INTRINSIC LOCAL CONSTITUENTS; POTENTIAL-ENERGY CURVE; MINIMAL BASIS-SETS; KINETIC-ENERGY; CHEMICAL-BOND; GROUND-STATE; HYDROGEN MOLECULE; WAVE-FUNCTIONS; BINDING C1 [Schmidt, Michael W.; Ruedenberg, Klaus] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Schmidt, Michael W.; Ruedenberg, Klaus] Iowa State Univ, Ames Lab USDOE, Ames, IA 50011 USA. [Ivanic, Joseph] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Schmidt, MW (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. NR 73 TC 7 Z9 7 U1 1 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-66469-6; 978-3-527-33314-1 PY 2014 BP 1 EP 67 D2 10.1002/9783527664696 PG 67 WC Chemistry, Physical SC Chemistry GA BC5CK UT WOS:000353166600002 ER PT J AU Seam, N Suffredini, AF AF Seam, Nitin Suffredini, Anthony F. TI Is antithrombin treatment of disseminated intravascular coagulation a quixotic goal? SO CRITICAL CARE LA English DT Editorial Material ID INTERNATIONAL SOCIETY; ANTICOAGULANT-THERAPY; SEVERE SEPSIS; HARMONIZED GUIDANCE; BLEEDING RISK; HEMOSTASIS; THROMBOSIS; JAPAN; SUPPLEMENTATION; EFFICACY AB The development of disseminated intravascular coagulation (DIC) is associated with increased sepsis mortality. Antithrombin (AT) is one of several anticoagulants that have been studied in randomized trials of sepsis without benefit. In a recent study, Iba and colleagues reviewed data from patients who were treated for sepsis-related DIC with two lower doses of AT concentrate than studied in prior trials. Patients received 1,500 IU/day (n = 259) or 3,000 IU/day (n = 48) of AT for 3 days. All patients had baseline antithrombin activity <40% and there was no placebo group. The AT 3,000 group had higher 28-day survival as well as a higher rate of DIC resolution than the AT 1,500 group. Though intriguing, the study findings are limited by the non-randomized retrospective nature of the findings, which resulted in baseline differences in multiple confounders that affect mortality, as well as the lack of a placebo group to compare outcomes. C1 [Seam, Nitin] Vet Affairs Med Ctr, Pulm Sect, Washington, DC 20442 USA. [Seam, Nitin; Suffredini, Anthony F.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Suffredini, AF (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. EM asuffredini@cc.nih.gov FU Intramural NIH HHS NR 16 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 6 AR 639 DI 10.1186/s13054-014-0639-1 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA CI9LV UT WOS:000355092500053 PM 25673027 ER PT J AU Brady, OJ Messina, JP Scott, TW Hay, SI AF Brady, Oliver J. Messina, Jane P. Scott, Thomas W. Hay, Simon I. BE Gubler, DJ Ooi, EE Vasudevan, S Farrar, J TI Mapping the Epidemiology of Dengue SO DENGUE AND DENGUE HEMORRHAGIC FEVER, 2ND EDITION LA English DT Article; Book Chapter ID AEDES-AEGYPTI DIPTERA; DOMINANT ANOPHELES VECTORS; HEALTH-ORGANIZATION DEFINITION; LIFE TABLE MODEL; RIO-DE-JANEIRO; CLIMATE-CHANGE; HEMORRHAGIC-FEVER; DISTRIBUTION MAPS; BIONOMIC PRECIS; HUMAN MALARIA C1 [Brady, Oliver J.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Messina, Jane P.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA. [Scott, Thomas W.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Brady, OJ (reprint author), Univ Oxford, Dept Zool, Tinbergen Bldg,South Pk Rd, Oxford OX1 3PS, England. EM oliver.brady@zoo.ox.ac.uk; jane.messina@gmail.com; twscott@ucdavis.edu; simon.hay@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; Brady, Oliver/0000-0002-3235-2129 NR 102 TC 1 Z9 1 U1 0 U2 3 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-964-9 PY 2014 BP 30 EP 49 D2 10.1079/9781845939649.0000 PG 20 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BC7RW UT WOS:000355179000004 ER PT J AU Perkins, TA Reiner, RC Rodriguez-Barraquer, I Smith, DL Scott, TW Cummings, DAT AF Perkins, T. Alex Reiner, Robert C., Jr. Rodriguez-Barraquer, Isabel Smith, David L. Scott, Thomas W. Cummings, Derek A. T. BE Gubler, DJ Ooi, EE Vasudevan, S Farrar, J TI A Review of Transmission Models of Dengue: A Quantitative and Qualitative Analysis of Model Features SO DENGUE AND DENGUE HEMORRHAGIC FEVER, 2ND EDITION LA English DT Review; Book Chapter ID ANTIBODY-DEPENDENT ENHANCEMENT; VECTOR AEDES-AEGYPTI; POPULATION-DYNAMICS; VIRUS TRANSMISSION; SIMULATION-MODEL; HUMAN MOVEMENT; FEVER; MOSQUITO; EPIDEMIOLOGY; PERSISTENCE C1 [Perkins, T. Alex; Reiner, Robert C., Jr.; Smith, David L.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Perkins, T. Alex; Reiner, Robert C., Jr.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA. [Rodriguez-Barraquer, Isabel; Cummings, Derek A. T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Perkins, TA (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM taperkins@ucdavis.edu; rcreiner@ucdavis.edu; irodrigu@jhsph.edu; dlsmith@jhsph.edu; twscott@ucdavis.edu; dcumming@jhsph.edu NR 62 TC 3 Z9 3 U1 1 U2 3 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-964-9 PY 2014 BP 99 EP 114 D2 10.1079/9781845939649.0000 PG 16 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BC7RW UT WOS:000355179000008 ER PT J AU Sim, S Cirimotich, CM Ramirez, JL Souza-Neto, JA Dimopoulos, G AF Sim, Shuzhen Cirimotich, Christopher M. Ramirez, Jose L. Souza-Neto, Jayme A. Dimopoulos, George BE Gubler, DJ Ooi, EE Vasudevan, S Farrar, J TI Dengue Virus-Mosquito Interactions and Molecular Methods of Vector Control SO DENGUE AND DENGUE HEMORRHAGIC FEVER, 2ND EDITION LA English DT Article; Book Chapter ID QUANTITATIVE TRAIT LOCI; AEDES-AEGYPTI POPULATIONS; LIFE-SHORTENING WOLBACHIA; ODORANT-BINDING-PROTEIN; GRAM-POSITIVE BACTERIA; RNA INTERFERENCE; ANOPHELES-GAMBIAE; GLOBAL DISTRIBUTION; ANTIVIRAL RESPONSE; HEMORRHAGIC-FEVER C1 [Sim, Shuzhen] Genome Inst Singapore, Singapore 138672, Singapore. [Cirimotich, Christopher M.] Battelle Mem Inst, Charlottesville, VA 22911 USA. [Ramirez, Jose L.] NIH, USA Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Souza-Neto, Jayme A.] Oswaldo Cruz Fdn Fiocruz, Ctr Technol Dev Hlth CDTS, BR-21040360 Rio De Janeiro, Brazil. [Dimopoulos, George] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Sim, S (reprint author), Genome Inst Singapore, 60 Biopolis St,02-01 Genome, Singapore 138672, Singapore. EM shuzhens@gis.a-star.edu.sg; cirimotichc@battelle.org; ramirezjl@niaid.nih.gov; jneto@cdts.fiocruz.br; gdimopou@jhsph.edu NR 129 TC 0 Z9 0 U1 3 U2 3 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-964-9 PY 2014 BP 425 EP 441 D2 10.1079/9781845939649.0000 PG 17 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BC7RW UT WOS:000355179000024 ER PT S AU Vorontsov, E Abi-Jaoudeh, N Kadoury, S AF Vorontsov, Eugene Abi-Jaoudeh, Nadine Kadoury, Samuel BE Yoshida, H Nappi, JJ Saini, S TI Metastatic Liver Tumor Segmentation Using Texture-Based Omni-Directional Deformable Surface Models SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Segmentation; Deformable model; GLCM; SVM; Tumor; Liver; CT image AB The delineation of tumor boundaries is an essential task for the diagnosis and follow-up of liver cancer. However accurate segmentation remains challenging due to tissue inhomogeneity and high variability in tumor appearance. In this paper, we propose a semi-automatic liver tumor segmentation method that combines a deformable model with a machine learning mechanism. More precisely, segmentation is performed by an MRF-based omni-directional deformable surface model that uses image information together with a two-class (tumor, non-tumor) voxel classification map. The classification map is produced by a kernel SVM classifier trained on texture features, as well as intensity mean and variance. The segmentation method is validated on a metastatic tumor dataset consisting of 27 tumors across a set of abdominal CT images, using leave-one-out validation. Compared to pure voxel and gradient approaches, our method achieves better performance in terms of mean distance and Dice scores on the group of 27 liver tumors and can deal with highly pathological cases. C1 [Vorontsov, Eugene; Kadoury, Samuel] Ecole Polytech Montreal, MEDICAL, Montreal, PQ, Canada. [Abi-Jaoudeh, Nadine] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Kadoury, S (reprint author), Ecole Polytech Montreal, MEDICAL, Montreal, PQ, Canada. EM eugene.vorontsov@polymtl.ca; abijaoudehn@cc.nih.gov; samuel.kadoury@polymtl.ca NR 12 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 74 EP 83 DI 10.1007/978-3-319-13692-9_7 PG 10 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800007 ER PT S AU Farag, A Lu, L Turkbey, E Liu, JM Summers, RM AF Farag, Amal Lu, Le Turkbey, Evrim Liu, Jiamin Summers, Ronald M. BE Yoshida, H Nappi, JJ Saini, S TI A Bottom-Up Approach for Automatic Pancreas Segmentation in Abdominal CT Scans SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Pancreas; Random forest; CT; Hierarchical two-tiered information propagation AB Organ segmentation is a prerequisite for a computer-aided diagnosis (CAD) system to detect pathologies and perform quantitative analysis. For anatomically high-variability abdominal organs such as the pancreas, previous segmentation works report low accuracies when comparing to organs like the heart or liver. In this paper, a fully-automated bottom-up method is presented for pancreas segmentation, using abdominal computed tomography (CT) scans. The method is based on a hierarchical two-tiered information propagation by classifying image patches. It labels superpixels as pancreas or not via pooling patch-level confidences on 2D CT slices over-segmented by the Simple Linear Iterative Clustering approach. A supervised random forest (RF) classifier is trained on the patch level and a two-level cascade of RFs is applied at the superpixel level, coupled with multi-channel feature extraction, respectively. On six-fold cross-validation using 80 patient CT volumes, we achieved 68.8 % Dice coefficient and 57.2 % Jaccard Index, comparable to or slightly better than published state-of-the-art methods. C1 [Farag, Amal; Lu, Le; Turkbey, Evrim; Liu, Jiamin; Summers, Ronald M.] Natl Inst Hlth Clin Ctr, Dept Radiol & Imaging Sci, Imaging Biomarkers & CAD Lab, Bethesda, MD 20892 USA. RP Farag, A (reprint author), Natl Inst Hlth Clin Ctr, Dept Radiol & Imaging Sci, Imaging Biomarkers & CAD Lab, Bld 10 Rm 1C224D, Bethesda, MD 20892 USA. EM amal.aly1@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 103 EP 113 DI 10.1007/978-3-319-13692-9_10 PG 11 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800010 ER PT J AU Faria, NR Rambaut, A Suchard, MA Baele, G Bedford, T Ward, MJ Tatem, AJ Sousa, JD Arinaminpathy, N Pepin, J Posada, D Peeters, M Pybus, OG Lemey, P AF Faria, N. R. Rambaut, A. Suchard, M. A. Baele, G. Bedford, T. Ward, M. J. Tatem, A. J. Sousa, J. D. Arinaminpathy, N. Pepin, J. Posada, D. Peeters, M. Pybus, O. G. Lemey, P. TI Establishment and early spread of the AIDS pandemic SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on Antiviral Drug Resistance - Meeting the Global Challenge CY JUN 03-07, 2014 CL Berlin, GERMANY C1 [Faria, N. R.; Arinaminpathy, N.; Pybus, O. G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Faria, N. R.; Baele, G.; Sousa, J. D.; Lemey, P.] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, B-3000 Leuven, Belgium. [Rambaut, A.; Ward, M. J.] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland. [Rambaut, A.; Tatem, A. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Suchard, M. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, M. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Suchard, M. A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Bedford, T.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA. [Tatem, A. J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. [Pepin, J.] Univ Sherbrooke, Dept Microbiol & Infect Dis, Sherbrooke, PQ J1H 5N4, Canada. [Posada, D.] Univ Vigo, Dept Biochem Genet & Immunol, Vigo 36310, Spain. [Peeters, M.] Inst Rech Dev, Lab Retrovirus, F-34032 Montpellier, France. RI Posada, David/C-4502-2008 OI Posada, David/0000-0003-1407-3406 NR 0 TC 1 Z9 1 U1 0 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 1 MA P5 BP A7 EP A7 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CH9TW UT WOS:000354380300006 ER PT J AU Kearney, MF Spindler, J Shao, W Kordella, D Stewart, C Haubrich, R Riddler, S Lalama, C Hughes, M Coffin, JM Mellors, JW AF Kearney, M. F. Spindler, J. Shao, W. Kordella, D. Stewart, C. Haubrich, R. Riddler, S. Lalama, C. Hughes, M. Coffin, J. M. Mellors, J. W. TI Is pre-ART intra-patient HIV-1 diversity associated with virologic failure and drug resistance on cART? SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on Antiviral Drug Resistance - Meeting the Global Challenge CY JUN 03-07, 2014 CL Berlin, GERMANY C1 [Kearney, M. F.; Spindler, J.; Kordella, D.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Shao, W.] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [Haubrich, R.] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. [Riddler, S.] Univ Pittsburgh, Infect Dis Div, Pittsburgh, PA USA. [Hughes, M.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Coffin, J. M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Mellors, J. W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 1 MA 111 BP A157 EP A157 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CH9TW UT WOS:000354380300136 ER PT J AU Kireev, DE Grossman, Z Lopatuxin, AE Kanev, AN Maksyutov, AZ Varticovski, L Shao, W Maldarelli, F AF Kireev, D. E. Grossman, Z. Lopatuxin, A. E. Kanev, A. N. Maksyutov, A. Z. Varticovski, L. Shao, W. Maldarelli, F. TI Analysis of HIV transmission in the Russian Federation SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on Antiviral Drug Resistance - Meeting the Global Challenge CY JUN 03-07, 2014 CL Berlin, GERMANY C1 [Grossman, Z.; Varticovski, L.; Maldarelli, F.] NCI, NIH, Bethesda, MD 20892 USA. [Shao, W.] Leidos Inc, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 1 MA 37 BP A68 EP A68 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CH9TW UT WOS:000354380300062 ER PT B AU Wang, MY Deshpande, DA AF Wang, Mingyi Deshpande, Deepak A. BE Rojas, M Meiners, S LeSaux, CJ TI Mouse Models to Explore the Aging Lung SO MOLECULAR ASPECTS OF AGING: UNDERSTANDING LUNG AGING LA English DT Article; Book Chapter ID OBSTRUCTIVE PULMONARY-DISEASE; LIFE-SPAN EXTENSION; AGE-RELATED-CHANGES; ALPHA-MUPA MICE; CIGARETTE-SMOKE; OXIDATIVE STRESS; KNOCKOUT MICE; CALORIC RESTRICTION; RECEPTOR KNOCKOUT; AIRWAY-RESISTANCE C1 [Wang, Mingyi] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Deshpande, Deepak A.] Univ Maryland, Sch Med, Pulm & Crit Care Med Div, Baltimore, MD 21201 USA. RP Wang, MY (reprint author), NIA, Intramural Res Program, Baltimore, MD 21224 USA. NR 101 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA BN 978-1-118-39629-2; 978-1-118-39624-7 PY 2014 BP 117 EP 129 D2 10.1002/9781118396292 PG 13 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Respiratory System SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Respiratory System GA BC7KZ UT WOS:000354980500010 ER PT B AU Fitzhugh, D Cohen, SG Evans, R AF Fitzhugh, David Cohen, Sheldon G. Evans, Richard, III BE Lockey, RF Ledford, DK TI Allergen Immunotherapy in a Historical Perspective SO ALLERGENS AND ALLERGEN IMMUNOTHERAPY: SUBCUTANEOUS, SUBLINGUAL,AND ORAL, 5TH EDITION LA English DT Article; Book Chapter ID HAY-FEVER PATIENTS; BRONCHIAL-ASTHMA; HYPOSENSITIZATION THERAPY; SUBLINGUAL IMMUNOTHERAPY; DERMATITIS VENENATA; PENICILLIN ALLERGY; BACTERIAL VACCINES; CONTROLLED-TRIAL; POLLEN ALLERGY; RAGWEED POLLEN C1 [Fitzhugh, David] Allergy Partners Chapel Hill, Chapel Hill, NC 27599 USA. [Cohen, Sheldon G.] NIAID, NIH, Bethesda, MD 20892 USA. [Evans, Richard, III] Childrens Mem Hosp, Div Allergy, Chicago, IL 60614 USA. RP Fitzhugh, D (reprint author), Allergy Partners Chapel Hill, Chapel Hill, NC 27599 USA. NR 221 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84214-574-6; 978-1-84214-573-9 PY 2014 BP 3 EP 23 PG 21 WC Allergy; Immunology SC Allergy; Immunology GA BC3RG UT WOS:000351872300002 ER PT J AU Grant, PM Sheikh, V DerSimonian, R Sneller, M Brown, TT Sereti, I AF Grant, P. M. Sheikh, V. DerSimonian, R. Sneller, M. Brown, T. T. Sereti, I. TI The relationship between corticosteroid use and advanced HIV on bone turnover after ART initiation SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International Workshop on Co-Morbidities and Adverse Drug Reaction in HIV CY OCT 06-08, 2014 CL Philadelphia, PA C1 [Grant, P. M.] Stanford Univ, Stanford, CA 94305 USA. [Sheikh, V.; DerSimonian, R.; Sneller, M.; Sereti, I.] NIAID, NIH, Bethesda, MD 20892 USA. [Brown, T. T.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 2 MA 017 BP A15 EP A16 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CI2TP UT WOS:000354600300018 ER PT J AU Hadigan, C Thiara, DK Howard, L Lui, CY Raman, F Mangat, S Purdy, JB Sibley, CT Bluemke, DA AF Hadigan, C. Thiara, D. K. Howard, L. Lui, C. Y. Raman, F. Mangat, S. Purdy, J. B. Sibley, C. T. Bluemke, D. A. TI Impaired cardiac strain and biomarkers of immune activation in HIV SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International Workshop on Co-Morbidities and Adverse Drug Reaction in HIV CY OCT 06-08, 2014 CL Philadelphia, PA C1 [Hadigan, C.; Thiara, D. K.; Howard, L.; Lui, C. Y.; Raman, F.; Mangat, S.; Purdy, J. B.; Bluemke, D. A.] NIH, Bethesda, MD 20892 USA. [Sibley, C. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 2 MA O08 BP A8 EP A9 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CI2TP UT WOS:000354600300009 ER PT J AU Unsal, AB Abd-Elmoniem, KZ Rupert, A Kovacs, J Purdy, JB Hazra, R Gharib, AM Hadigan, CM AF Unsal, A. B. Abd-Elmoniem, K. Z. Rupert, A. Kovacs, J. Purdy, J. B. Hazra, R. Gharib, A. M. Hadigan, C. M. TI T-cell activation and E-selectin associated with coronary plaque in HIV-infected youth SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International Workshop on Co-Morbidities and Adverse Drug Reaction in HIV CY OCT 06-08, 2014 CL Philadelphia, PA C1 [Unsal, A. B.; Abd-Elmoniem, K. Z.; Rupert, A.; Kovacs, J.; Purdy, J. B.; Hazra, R.; Gharib, A. M.; Hadigan, C. M.] NIH, Bethesda, MD 20892 USA. RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008 OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem, Khaled/0000-0002-1001-1702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 2 MA P22 BP A42 EP A42 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CI2TP UT WOS:000354600300047 ER PT J AU Unsal, AB Abd-Elmoniem, KZ Rupert, A Kovacs, J Purdy, JB Hazra, R Gharib, AM Hadigan, CM AF Unsal, A. B. Abd-Elmoniem, K. Z. Rupert, A. Kovacs, J. Purdy, J. B. Hazra, R. Gharib, A. M. Hadigan, C. M. TI T-cell activation and E-selectin associated with coronary plaque in HIV-infected youth SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International Workshop on Co-Morbidities and Adverse Drug Reaction in HIV CY OCT 06-08, 2014 CL Philadelphia, PA C1 [Unsal, A. B.; Abd-Elmoniem, K. Z.; Rupert, A.; Kovacs, J.; Purdy, J. B.; Hazra, R.; Gharib, A. M.; Hadigan, C. M.] NIH, Bethesda, MD 20892 USA. RI Gharib, Ahmed/O-2629-2016 OI Gharib, Ahmed/0000-0002-2476-481X NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 SU 2 MA O06 BP A6 EP A8 PG 3 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CI2TP UT WOS:000354600300007 ER PT B AU Beutler, JA Cragg, GM Iwu, M Newman, DJ Okunji, C AF Beutler, John A. Cragg, Gordon M. Iwu, Maurice Newman, David J. Okunji, Christopher BA GuribFakim, A BF GuribFakim, A TI Anticancer Potential of African Plants: The Experience of the United States National Cancer Institute and National Institutes of Health SO NOVEL PLANT BIORESOURCES: APPLICATIONS IN FOOD, MEDICINE AND COSMETICS LA English DT Article; Book Chapter ID MADAGASCAR RAIN-FOREST; ANTIBODY-DRUG CONJUGATE; CYTOTOXIC CLERODANE DITERPENOIDS; NATURAL-PRODUCTS; DRY FOREST; ANTIPROLIFERATIVE COMPOUNDS; BIODIVERSITY CONSERVATION; ERYTHROXYLUM-PERVILLEI; CELL-GROWTH; ANCISTROCLADUS-KORUPENSIS C1 [Beutler, John A.] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Cragg, Gordon M.; Newman, David J.] NCI Frederick, Nat Prod Branch, Dev Therapeut Program, Frederick, MD USA. [Iwu, Maurice] Bioresource Dev & Conservat Programme, Head Off, Abuja, FCT, Nigeria. [Okunji, Christopher] US Pharmacopeial Convent Inc, Rockville, MD USA. RP Beutler, JA (reprint author), NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 135 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-46056-6; 978-1-118-46061-0 PY 2014 BP 133 EP 149 PG 17 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA BC6XA UT WOS:000354551100011 ER PT J AU Chung, T Hilton, M AF Chung, Tammy Hilton, Michael TI Alcohol Research and eHealth Technology SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material ID HEALTH C1 [Chung, Tammy] Univ Pittsburgh, Dept Psychiat, Psychiat & Epidemiol, Pittsburgh, PA 15260 USA. [Hilton, Michael] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. RP Chung, T (reprint author), Univ Pittsburgh, Dept Psychiat, Psychiat & Epidemiol, Pittsburgh, PA 15260 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2014 VL 36 IS 1 BP 1 EP 4 PG 4 WC Substance Abuse SC Substance Abuse GA CH2MG UT WOS:000353858700001 PM 26280036 ER PT J AU Arora, S Yttri, J Nilsen, W AF Arora, Shifali Yttri, Jennifer Nilsen, Wendy TI Privacy and Security in Mobile Health (mHealth) Research SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Review DE Alcohol use, abuse, and dependence; problematic alcohol use; alcohol use disorders; mobile health; mHealth; wireless technology; mobile devices; sensors; data collection; intervention; privacy; security AB Research on the use of mobile technologies for alcohol use problems is a developing field. Rapid technological advances in mobile health (or mHealth) research generate both opportunities and challenges, including how to create scalable systems capable of collecting unprecedented amounts of data and conducting interventions some in real time while at the same time protecting the privacy and safety of research participants. Although the research literature in this area is sparse, lessons can be borrowed from other communities, such as cybersecurity or Internet security, which offer many techniques to reduce the potential risk of data breaches or tampering in mHealth. More research into measures to minimize risk to privacy and security effectively in mHealth is needed. Even so, progress in mHealth research should not stop while the field waits for perfect solutions. C1 [Arora, Shifali; Yttri, Jennifer] Natl Sci Fdn, Directorate Comp & Informat Sci & Engn, Washington, DC 20550 USA. [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Arora, S (reprint author), Natl Sci Fdn, Directorate Comp & Informat Sci & Engn, Washington, DC 20550 USA. NR 23 TC 5 Z9 5 U1 0 U2 6 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2014 VL 36 IS 1 BP 143 EP 150 PG 8 WC Substance Abuse SC Substance Abuse GA CH2MG UT WOS:000353858700015 PM 26259009 ER PT B AU Roschewski, M Wilson, W AF Roschewski, Mark Wilson, Wyndham BE Abutalib, SA Markman, M TI Burkitt lymphoma SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter C1 [Roschewski, Mark; Wilson, Wyndham] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roschewski, M (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 286 EP 289 D2 10.1002/9781118589199 PG 4 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800045 ER PT B AU Dunleavy, K AF Dunleavy, Kieron BE Abutalib, SA Markman, M TI HIV-associated lymphoma SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID NON-HODGKIN-LYMPHOMA; CHEMOTHERAPY C1 NCI, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 304 EP 307 D2 10.1002/9781118589199 PG 4 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800048 ER PT B AU Gramza, AW AF Gramza, Ann W. BE Abutalib, SA Markman, M TI Endocrine malignancies SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID THYROID-CANCER C1 NCI, NIH, Endocrine Oncol Branch, Bethesda, MD 20892 USA. RP Gramza, AW (reprint author), NCI, NIH, Endocrine Oncol Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 476 EP 479 D2 10.1002/9781118589199 PG 4 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800074 ER PT B AU Pinto, P AF Pinto, Peter BE Abutalib, SA Markman, M TI Surgical aspects of prostate cancer SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID RADICAL PROSTATECTOMY C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pinto, P (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 747 EP 753 D2 10.1002/9781118589199 PG 7 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800116 ER PT B AU Heery, CR Gulley, JL AF Heery, Christopher R. Gulley, James L. BE Abutalib, SA Markman, M TI Nuts and bolts of cancer immunotherapy SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID PROSTATE-CANCER C1 [Heery, Christopher R.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gulley, James L.] NCI, Med Oncol Serv, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Heery, CR (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 826 EP 830 D2 10.1002/9781118589199 PG 5 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800130 ER PT B AU Curtis, JM Knowler, WC AF Curtis, Jeffrey M. Knowler, William C. BE Lamster, IB TI Classification, epidemiology, diagnosis, and risk factors of diabetes SO DIABETES MELLITUS AND ORAL HEALTH: AN INTERPROFESSIONAL APPROACH LA English DT Article; Book Chapter ID IMPAIRED GLUCOSE-TOLERANCE; SWEDISH OBESE SUBJECTS; BETA-CELL FUNCTION; PIMA INDIAN WOMEN; INSULIN-RESISTANCE; BARIATRIC SURGERY; EXPERT COMMITTEE; HISPANIC WOMEN; LIFE-STYLE; PREVENTION C1 [Curtis, Jeffrey M.; Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85016 USA. RP Curtis, JM (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85016 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-37780-2; 978-1-118-86416-6 PY 2014 BP 27 EP 44 D2 10.1002/9781118887837 PG 18 WC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism SC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism GA BC3FZ UT WOS:000351620800003 ER PT B AU Shah, SK AF Shah, Seema K. BE Cohen, IG Lynch, HF TI Outsourcing Ethical Obligations: Should the Revised Common Rule Address the Responsibilities of Investigators and Sponsors? SO HUMAN SUBJECTS RESEARCH REGULATION: PERSPECTIVES ON THE FUTURE SE Basic Bioethics LA English DT Article; Book Chapter ID INTERNATIONAL CONSENSUS OPINION; CLINICAL-RESEARCH; EXPRESSIVE FUNCTION; CARE DEBATE; STANDARD; BEDSIDE; BENCH; LAW C1 [Shah, Seema K.] NIH, Clin Ctr Dept Bioeth, Bethesda, MD 20892 USA. [Shah, Seema K.] NIH, Div Aids, Bethesda, MD USA. RP Shah, SK (reprint author), NIH, Clin Ctr Dept Bioeth, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-52621-0; 978-0-262-02746-5 J9 BASIC BIOETH PY 2014 BP 127 EP 141 D2 10.7551/mitpress/9780262027465.001.0001 PG 15 WC Ethics; Law; Medical Ethics SC Social Sciences - Other Topics; Government & Law; Medical Ethics GA BC5SH UT WOS:000353523300013 ER PT B AU Weil, C Shutak, H Fombonne, B Lockhart, N AF Weil, Carol Shutak, Hilary Fombonne, Benjamin Lockhart, Nicole BE Cohen, IG Lynch, HF TI Mandating Consent for Future Research with Biospecimens: A Call for Enhanced Community Engagement SO HUMAN SUBJECTS RESEARCH REGULATION: PERSPECTIVES ON THE FUTURE SE Basic Bioethics LA English DT Article; Book Chapter ID INFORMED-CONSENT; ADVISORY BOARDS; PERSPECTIVES; PARTICIPANTS; SAMPLES C1 [Weil, Carol] NCI, Eth & Regulatory Affairs, Bethesda, MD 20892 USA. [Shutak, Hilary] Natl Inst Diabet & Digest & Kidney Dis, Off Commun & Publ Liaison, Bethesda, MD USA. [Fombonne, Benjamin] NCI, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Lockhart, Nicole] NHGRI, Div Genom & Soc, Bethesda, MD USA. RP Weil, C (reprint author), NCI, Eth & Regulatory Affairs, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-52621-0; 978-0-262-02746-5 J9 BASIC BIOETH PY 2014 BP 221 EP 235 D2 10.7551/mitpress/9780262027465.001.0001 PG 15 WC Ethics; Law; Medical Ethics SC Social Sciences - Other Topics; Government & Law; Medical Ethics GA BC5SH UT WOS:000353523300020 ER PT S AU Schug, TT Birnbaum, LS AF Schug, Thaddeus T. Birnbaum, Linda S. BE Snedeker, SM TI Human Health Effects of Bisphenol A SO TOXICANTS IN FOOD PACKAGING AND HOUSEHOLD PLASTICS: EXPOSURE AND HEALTH RISKS TO CONSUMERS SE Molecular and Integrative Toxicology LA English DT Article; Book Chapter DE Bisphenol A; Endocrine disruption; Developmental toxicity; Pharmacokinetics; Biomonitoring ID IN-VITRO FERTILIZATION; ENDOCRINE-DISRUPTING CHEMICALS; ARYL-HYDROCARBON RECEPTOR; HUMAN EXPOSURE; BREAST-CANCER; ESTROGENIC CHEMICALS; MAMMARY-GLAND; ENVIRONMENTAL CHEMICALS; COMPOSITE RESTORATIONS; HORMONE CONCENTRATIONS AB Bisphenol A (BPA) is a high production endocrine disrupting chemical found in numerous consumer products. BPA has been used commercially since 1957 to make hard polycarbonate plastics and epoxy resins used in food-can linings, cash-register receipts, and dental resins. The ubiquity of BPA in our environment results in exposure to this chemical daily in human populations. But controversy remains regarding how much BPA humans actually ingest or otherwise encounter. Many laboratory animal and human studies have linked exposures to BPA, a hormone mimicking chemical, to adverse health effects, including altered behavior and obesity in children, reproductive abnormalities, cardiovascular changes, and various cancers. However, there have been considerable inconsistencies in the outcomes from these studies with respect to the nature of the adverse health effects observed, and questions as to whether the BPA dose at which they occur are within the range of non-occupational human exposures. This chapter reviews the latest research on BPA, focusing on human exposure, discussions of biomonitoring studies and toxicokinetic models, human health effects, and research needs. We also include illustrative examples of animal models that address whether BPA-exposure is associated with changes in certain health endpoints. C1 [Schug, Thaddeus T.] NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NCI, NIH, Res Triangle Pk, NC USA. RP Schug, TT (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA. EM schugt2@niehs.nih.gov; birnbaumls@niehs.nih.gov NR 118 TC 3 Z9 3 U1 2 U2 10 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND SN 2168-4219 BN 978-1-4471-6500-2; 978-1-4471-6499-9 J9 MOLEC INTEGR TOXICOL PY 2014 BP 1 EP 29 DI 10.1007/978-1-4471-6500-2_1 D2 10.1007/978-1-4471-6500-2 PG 29 WC Environmental Sciences; Food Science & Technology; Toxicology SC Environmental Sciences & Ecology; Food Science & Technology; Toxicology GA BC6BJ UT WOS:000353720200002 ER PT J AU Otto, P Sikdar, S Im, HS Gavelli, F AF Otto, Paul Sikdar, Siddhartha Im, Hyun Soo Gavelli, Frances GP IEEE TI Ultrasound Based Muscle Kinematics Measurement with Tracklet Stitching SO 2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY SEP 03-06, 2014 CL Chicago, IL SP IEEE DE ultrasound; tracklet; feature tracking; speckle ID SKELETAL-MUSCLE; OPTICAL-FLOW; MOTION; TRACKING AB The objective of this study is to develop and validate an ultrasound (US) tissue tracking algorithm for measuring muscle velocity. This algorithm is designed to (1) be applicable to a wide variety of muscles, (2) overcome the limitations of previously published methods that required visualization of complete muscle fascicles, and (3) use B-mode imagery from commercially-available equipment that can be applied in a clinical office-type setting. This is accomplished by combining multiple block based tracking methods and filtering their output tracklets to create a velocity estimate. The algorithm was validated with a combination of Field II and in vivo MR velocity measurements. The average rectus femoris displacement error for the US data (average of 12 cycles) ranged from 0.7 to 6.4mm for flexion displacement and from 1.4 to 8.0mm during extension. C1 [Otto, Paul; Sikdar, Siddhartha] George Mason Univ, Dept Elect & Comp Engn, Fairfax, VA 22030 USA. [Im, Hyun Soo; Gavelli, Frances] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Otto, P (reprint author), George Mason Univ, Dept Elect & Comp Engn, Fairfax, VA 22030 USA. EM ssikdar@gmu.edu NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7049-0 PY 2014 BP 1884 EP 1887 DI 10.1109/ULTSYM.2014.0468 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BC4NN UT WOS:000352792500466 ER PT J AU Stofer, K Che, X AF Stofer, Kathryn Che, Xuan TI Comparing Experts and Novices on Scaffolded Data Visualizations using Eye-tracking SO JOURNAL OF EYE MOVEMENT RESEARCH LA English DT Article DE Scientific data visualizations; expert-novice; scaffolding; meaning-making; eye-tracking ID PHYSICS PROBLEMS; MAPS; PERFORMANCE; USERS; CATEGORIZATION; INFORMATION; MOVEMENTS; STUDENTS; BEHAVIOR; LEARN AB Spatially-based scientific data visualizations are becoming widely available, yet they are often not optimized for novice audiences. This study follows after an investigation of expert and novice meaning-making from scaffolded data visualizations using clinical interviews. Using eye-tracking and concurrent interviewing, we examined quantitative fixation and AOI data and qualitative scan path data for two expertise groups (N = 20) on five versions of scaffolded global ocean data visualizations. We found influences of expertise, scaffolding, and trial. In accordance with our clinical interview findings, experts use different meaning-making strategies from novices, but novice performance improves with scaffolding and guided practice, providing triangulation. Eye-tracking data also provide insight on meaning-making and effectiveness of scaffolding that clinical interviews alone did not. C1 [Stofer, Kathryn] Univ Florida, Gainesville, FL 32611 USA. [Che, Xuan] NIH, Bethesda, MD USA. RP Stofer, K (reprint author), Univ Florida, Gainesville, FL 32611 USA. RI Stofer, Kathryn/D-3946-2012 OI Stofer, Kathryn/0000-0002-3659-490X FU National Science Foundation [1114741]; Curtis and Isabella Holt Marine Education Award FX The authors wish to thank Shawn Rowe, Anthony Hornof, and Christy Steffke for assistance with and consultation on this research, two anonymous reviewers for feedback on this manuscript, and SMI for technical support. This work was supported by the National Science Foundation grant 1114741 to Shawn Rowe and a Curtis and Isabella Holt Marine Education Award to Kathryn Stofer. NR 66 TC 3 Z9 3 U1 6 U2 8 PU INT GROUP EYE MOVEMENT RESEARCH PI IFFWIL PA C/O RUDOLF GRONER, AL NASEEM ARABIAN STUD, IFFWIL, CH-3305, SWITZERLAND SN 1995-8692 J9 J EYE MOVEMENT RES JI J. Eye Mov. Res. PY 2014 VL 7 IS 5 AR 2 PG 15 WC Ophthalmology SC Ophthalmology GA CF9ER UT WOS:000352866400001 ER PT S AU Galperin, MY Koonin, EV AF Galperin, Michael Y. Koonin, Eugene V. BE Dediu, AH MartinVide, C Truthe, B TI Comparative Genomics Approaches to Identifying Functionally Related Genes SO ALGORITHMS FOR COMPUTATIONAL BIOLOGY SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 1st International Conference on Algorithms for Computational Biology (AlCoB) CY JUL 01-03, 2014 CL Tarragona, SPAIN SP Rovira i Virgili Univ, Res Grp Math Linguist DE genome annotation; genomic context; gene neighborhood; operon; functional genomics; orthology databases ID MOLECULAR INTERACTION DATABASE; PROTEIN-PROTEIN INTERACTIONS; TRANSCRIPTIONAL REGULATION; PROKARYOTIC GENOMES; 3-DIMENSIONAL STRUCTURE; DOMAIN INTERACTIONS; MICROBIAL GENOMES; REGULATORY SITES; FUSION EVENTS; COG DATABASE AB The rapid progress in genome sequencing makes it possible to address fundamental problems of biology and achieve critical insights into the functioning of the live cells and entire organisms. However, the widening gap between the rapidly accumulating sequence data and our ability to properly annotate these data constitutes a major problem that slows down the progress of genome biology. This paper discusses the notion of "function" as it relates to computational biology, lists the most common ways of assigning function to the new genes, particularly those that specifically rely on comparative genome analysis, and briefly reviews the drawbacks of the current algorithms for semi-automated high-throughput functional annotation of genomes. C1 [Galperin, Michael Y.; Koonin, Eugene V.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Galperin, MY (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM galperin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov NR 91 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-07953-0; 978-3-319-07952-3 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2014 VL 8542 BP 1 EP 24 PG 24 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BC4LQ UT WOS:000352635300001 ER PT S AU Mansoor, A Bagci, U Foster, B Xu, ZY Douglas, D Solomon, JM Udupa, JK Mollura, DJ AF Mansoor, Awais Bagci, Ulas Foster, Brent Xu, Ziyue Douglas, Deborah Solomon, Jeffrey M. Udupa, Jayaram K. Mollura, Daniel J. GP IEEE TI CIDI-Lung-Seg: A Single-Click Annotation Tool for Automatic Delineation of Lungs from CT Scans SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID FUZZY CONNECTEDNESS; IMAGE SEGMENTATION; THORACIC CT AB Accurate and fast extraction of lung volumes from computed tomography (CT) scans remains in a great demand in the clinical environment because the available methods fail to provide a generic solution due to wide anatomical variations of lungs and existence of pathologies. Manual annotation, current gold standard, is time consuming and often subject to human bias. On the other hand, current state-of-the-art fully automated lung segmentation methods fail to make their way into the clinical practice due to their inability to efficiently incorporate human input for handling misclassifications and praxis. This paper presents a lung annotation tool for CT images that is interactive, efficient, and robust. The proposed annotation tool produces an "'as accurate as possible" initial annotation based on the fuzzy-connectedness image segmentation, followed by efficient manual fixation of the initial extraction if deemed necessary by the practitioner. To provide maximum flexibility to the users, our annotation tool is supported in three major operating systems (Windows, Linux, and the Mac OS X). The quantitative results comparing our free software with commercially available lung segmentation tools show higher degree of consistency and precision of our software with a considerable potential to enhance the performance of routine clinical tasks. C1 [Mansoor, Awais; Bagci, Ulas; Foster, Brent; Xu, Ziyue; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Mansoor, A (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. OI Bagci, Ulas/0000-0001-7379-6829 NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 1087 EP 1090 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044701022 ER PT S AU Bulea, TC Kim, J Damiano, DL Stanley, CJ Park, HS AF Bulea, Thomas C. Kim, Jonghyun Damiano, Diane L. Stanley, Christopher J. Park, Hyung-Soon GP IEEE TI User-Driven Control Increases Cortical Activity during Treadmill Walking: An EEG Study SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID INDEPENDENT COMPONENT ANALYSIS; DESYNCHRONIZATION; TRIAL AB Treadmills provide a safe and efficient method for gait rehabilitation but treadmill based training paradigms have not been shown to create superior results when compared with traditional physical therapy methods such as overground training. One explanation for this may be that walking at a constant, fixed speed requires little mental engagement from the user, which has been postulated as a key factor in the success of motor learning. To increase mental engagement, we developed a user-driven treadmill control scheme. In this paper we use electroencephalography (EEG) to compare cortical activity during user-driven (active) walking with activity on a normal (passive) treadmill in nine healthy subjects. We used independent component analysis (ICA) to isolate brain activity from artifactual components. We fit equivalent dipole sources to each brain component and clustered these across subjects. Our analysis revealed that relative to the passive treadmill, active walking resulted in statistically significant decreases in spectral power, i.e. desynchronization, in the anterior cingulate, sensorimotor cortices, and posterior parietal lobe of the cortex. These results indicate that user-driven treadmills more fully engage the motor cortex and therefore could facilitate better training outcomes than a traditional treadmill. C1 [Bulea, Thomas C.; Damiano, Diane L.; Stanley, Christopher J.] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA. [Kim, Jonghyun] Daegu Gyeongbuk Inst Sci & Technol, Robot Engn Dept, Daegu, South Korea. [Park, Hyung-Soon] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. RP Bulea, TC (reprint author), NIH, Funct & Appl Biomech Sect, Bldg 10, Bethesda, MD 20892 USA. EM thomas.bulea@nih.gov; jhkim@dgist.ac.kr; damianod@cc.nih.gov; stanleycj@cc.nih.gov; hyungspark@kaist.ac.kr NR 21 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 2111 EP 2114 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702024 ER PT S AU Sargolzaei, S Goryawala, M Cabrerizo, M Chen, G Jayakar, P Duara, R Barker, W Adjouadi, M AF Sargolzaei, S. Goryawala, M. Cabrerizo, M. Chen, G. Jayakar, P. Duara, R. Barker, W. Adjouadi, M. GP IEEE TI Comparative Reliability Analysis of Publicly Available Software Packages for Automatic Intracranial Volume Estimation SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID MILD COGNITIVE IMPAIRMENT; ATROPHY; SEGMENTATION AB Intracranial volume is an important measure in brain research often used as a correction factor in inter subject studies. The current study investigates the resulting outcome in terms of the type of software used for automatically estimating ICV measure. Five groups of 70 subjects are considered, including adult controls (AC) (n=11), adult with dementia (AD) (n=11), pediatric controls (PC) (n=18) and two groups of pediatric epilepsy subjects (PE1.5 and PE3) (n=30) using 1.5 T and 3T scanners, respectively. Reference measurements were calculated for each subject by manually tracing intracranial cavity without sub-sampling. Four publicly available software packages (AFNI, Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the five groups. Linear regression analyses suggest that reference measurement discrepancy could be explained best by SPM [R-2 = 0. 67; p < 0.01] for the AC group, Freesurfer [R-2 = 0.46; p = 0.02] for the AD group, AFNI [R-2 = 0. 97; p < 0.01] for the PC group and FSL [R-2 = 0.6; p = 0. 1] for the PE1.5 and [R-2 = 0.6; p < 0.01] for PE3 groups. The study demonstrates that the choice of the automated software for ICV estimation is dependent on the population under consideration and whether the software used is atlas-based or not. C1 [Sargolzaei, S.; Goryawala, M.] Florida Int Univ, CATE, Miami, FL 33174 USA. [Cabrerizo, M.; Adjouadi, M.] Florida Int Univ, CATE, Dept Elect & Comp Engn, Miami, FL 33174 USA. [Chen, G.] NIMH, Sci & Stat Comp Core, NIH, HHS, Bethesda, MD 20892 USA. [Jayakar, P.] Miami Childrens Hosp, Inst Brain, Miami, FL 33155 USA. [Duara, R.; Barker, W.] Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami Beach, FL 33140 USA. RP Sargolzaei, S (reprint author), Florida Int Univ, CATE, Miami, FL 33174 USA. EM ssarg004@fiu.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 2342 EP 2345 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702081 ER PT S AU Cheng, R Turkbey, B Gandler, W Agarwal, HK Shah, VP Bokinsky, A McCreedy, E Wang, S Sankineni, S Bernardo, M Pohida, T Choyke, P McAuliffe, MJ AF Cheng, Ruida Turkbey, Baris Gandler, William Agarwal, Harsh K. Shah, Vijay P. Bokinsky, Alexandra McCreedy, Evan Wang, Shijun Sankineni, Sandeep Bernardo, Marcelino Pohida, Thomas Choyke, Peter McAuliffe, Matthew J. GP IEEE TI Atlas Based AAM and SVM Model for Fully Automatic MRI Prostate Segmentation SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID CLASSIFICATION AB Automatic prostate segmentation in MR images is a challenging task due to inter-patient prostate shape and texture variability, and the lack of a clear prostate boundary. We propose a supervised learning framework that combines the atlas based AAM and SVM model to achieve a relatively high segmentation result of the prostate boundary. The performance of the segmentation is evaluated with cross validation on 40 MR image datasets, yielding an average segmentation accuracy near 90%. C1 [Cheng, Ruida; Gandler, William; McCreedy, Evan; Pohida, Thomas; McAuliffe, Matthew J.] NIH, Ctr Informat Technol, Image Sci Lab, Bethesda, MD 20892 USA. [Turkbey, Baris; Agarwal, Harsh K.; Sankineni, Sandeep; Bernardo, Marcelino; Choyke, Peter] Natl Canc Inst, Mol Imaging Program, Bethesda, MD USA. [Bokinsky, Alexandra] Geometric Tools Inc, Chapel Hill, NC USA. [Wang, Shijun] NIH Clin Ctr, Imaging Biomarker & CAD Lab, Bethesda, MD USA. [Agarwal, Harsh K.] Philips Res NA, Briarcliff Manor, NY USA. [Shah, Vijay P.] VirtualScopics Inc, Rochester, NY USA. RP Cheng, R (reprint author), NIH, Ctr Informat Technol, Image Sci Lab, Bethesda, MD 20892 USA. EM ruida@mail.nih.gov RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X NR 15 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 2881 EP 2885 PG 5 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702216 ER PT S AU Xu, ZY Bagci, U Jonsson, C Jain, S Mollura, DJ AF Xu, Ziyue Bagci, Ulas Jonsson, Colleen Jain, Sanjay Mollura, Daniel J. GP IEEE TI Efficient Ribcage Segmentation from CT Scans Using Shape Features SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc DE Rib cage segmentation; multi-scale Hessian analysis; iterative relative fuzzy connectedness ID OBJECTS AB Rib cage structure and morphology is important for anatomical analysis of chest CT scans. A fundamental challenge in rib cage extraction is varying intensity levels and connection with adjacent bone structures including shoulder blade and sternum. In this study, we present a fully automated 3-D algorithm to segment the rib cage by detection and separation of other bone structures. The proposed approach consists of four steps. First, all high-intensity bone structures are segmented. Second, multi-scale Hessian analysis is performed to capture plateness and vesselness information. Third, with the plate/vessel features, bone structures other than rib cage are detected. Last, the detected bones are separated from rib cage with iterative relative fuzzy connectedness method. The algorithm was evaluated using 400 human CT scans and 100 small animal images with various resolution. The results suggested that the percent accuracy of rib cage extraction is over 95% with the proposed algorithm. C1 [Xu, Ziyue; Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Jonsson, Colleen] Univ Louisville, Louisville, KY 40292 USA. [Jain, Sanjay] Johns Hopkins Univ, Baltimore, MD USA. RP Xu, ZY (reprint author), NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. OI Bagci, Ulas/0000-0001-7379-6829 NR 10 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 2899 EP 2902 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702220 ER PT S AU Cheng, RD Xu, S Bokinsky, A McCreedy, E Gandler, W Wood, BJ McAuliffe, MJ AF Cheng, Ruida Xu, Sheng Bokinsky, Alexandra McCreedy, Evan Gandler, William Wood, Bradford J. McAuliffe, Matthew J. GP IEEE TI GPU Based Multi-histogram Volume Navigation for Virtual Bronchoscopy SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID IMAGES; CT; REAL AB An interactive navigation system for virtual bronchoscopy is presented, which is based solely on GPU based high performance multi-histogram volume rendering. C1 [Cheng, Ruida; McCreedy, Evan; Gandler, William; McAuliffe, Matthew J.] Ctr Informat Technol, Image Sci Lab, NIH, Bethesda, MD 20892 USA. RP Cheng, R (reprint author), Ctr Informat Technol, Image Sci Lab, NIH, Bethesda, MD 20892 USA. EM ruida@mail.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 3308 EP 3312 PG 5 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044703075 ER PT S AU Mansoor, A Bagci, U Mollura, DJ AF Mansoor, Awais Bagci, Ulas Mollura, Daniel J. GP IEEE TI Near-optimal Keypoint Sampling for Fast Pathological Lung Segmentation SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc AB Accurate delineation of pathological lungs from computed tomography (CT) images remains mostly unsolved because available methods fail to provide a reliable generic solution due to high variability of abnormality appearance. Local descriptor-based classification methods have shown to work well in annotating pathologies; however, these methods are usually computationally intensive which restricts their widespread use in real-time or near-real-time clinical applications. In this paper, we present a novel approach for fast, accurate, reliable segmentation of pathological lungs from CT scans by combining region-based segmentation method with local-descriptor classification that is performed on an optimized sampling grid. Our method works in two stages; during stage one, we adapted the fuzzy connectedness (FC) image segmentation algorithm to perform initial lung parenchyma extraction. In the second stage, texture-based local descriptors are utilized to segment abnormal imaging patterns using a near optimal keypoint analysis by employing centroid of supervoxel as grid points. The quantitative results show that our pathological lung segmentation method is fast, robust, and improves on current standards and has potential to enhance the performance of routine clinical tasks. C1 [Mansoor, Awais; Bagci, Ulas; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Bagci, U (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. OI Bagci, Ulas/0000-0001-7379-6829 NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6032 EP 6035 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706008 ER PT S AU Xu, ZY Bagci, U Jonsson, C Jain, S Mollura, DJ AF Xu, Ziyue Bagci, Ulas Jonsson, Colleen Jain, Sanjay Mollura, Daniel J. GP IEEE TI Accurate and Efficient Separation of Left and Right Lungs from 3D CT Scans: a Generic Hysteresis Approach SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc DE Left and right lung separation; hysteresis; Hessian; distance transform; lung segmentation AB Separation of left and right lungs from binary segmentation is often necessary for quantitative image-based pulmonary disease evaluation. In this article, we present a new fully automated approach for accurate, robust, and efficient lung separation using 3-D CT scans. Our method follows a hysteresis setting that utilizes information from both lung regions and background gaps. First, original segmentation is separated by subtracting the gaps between left and right lungs, which are enhanced with Hessian filtering. Second, the 2-D separation manifold in 3-D image space is estimated based on the distance information from the two subsets. Finally, the separation manifold is projected back to the original segmentation in order to produce the separated lungs through optimization for addressing minor local variations. An evaluation on over 400 human and 100 small animal 3-D CT images with various abnormalities is performed. The proposed scheme successfully separated all connections on the candidate CT images. Using hysteresis mechanism, each phase is performed robustly and 3-D information is utilized to achieve a generic, efficient, and accurate solution. C1 [Xu, Ziyue; Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Xu, ZY (reprint author), NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. OI Bagci, Ulas/0000-0001-7379-6829 NR 12 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6036 EP 6039 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706009 ER PT S AU Fukushima, M Saunders, RC Fujii, N Averbeck, BB Mishkin, M AF Fukushima, Makoto Saunders, Richard C. Fujii, Naotaka Averbeck, Bruno B. Mishkin, Mortimer GP IEEE TI Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID REPRESENTATION AB Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of 'Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production. C1 [Fukushima, Makoto; Saunders, Richard C.; Averbeck, Bruno B.; Mishkin, Mortimer] NIMH, Bethesda, MD 20892 USA. [Fujii, Naotaka] RIKEN, Brain Sci Inst, Saitama, Japan. RP Fukushima, M (reprint author), NIMH, Bethesda, MD 20892 USA. EM makoto.fukushima@nih.gov NR 20 TC 4 Z9 4 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6794 EP 6797 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706191 ER PT S AU Riley, WT Martin, CA Rivera, DE AF Riley, William T. Martin, Cesar A. Rivera, Daniel E. GP IEEE TI The Importance of Behavior Theory in Control System Modeling of Physical Activity Sensor Data SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc ID INTERVENTIONS; LIMITATIONS; TIME AB Among health behaviors, physical activity has the most extensive record of research using passive sensors. Control systems and other system dynamic approaches have long been considered applicable for understanding human behavior, but only recently has the technology provided the precise and intensive longitudinal data required for these analytic approaches. Although sensors provide intensive data on the patterns and variations of physical activity over time, the influences of these variations are often unmeasured. Health behavior theories provide an explanatory framework of the putative mediators of physical activity changes. Incorporating the intensive longitudinal measurement of these theoretical constructs is critical to improving the fit of control system model of physical activity and for advancing behavioral theory. Theory-based control models also provide guidance on the nature of the controllers which serve as the basis for just-in-time adaptive interventions based on these control system models. C1 [Riley, William T.] NCI, NIH, Bethesda, MD 20892 USA. [Martin, Cesar A.] Arizona State Univ, Sch Elect Comp & Energy Engn, Tempe, AZ USA. [Rivera, Daniel E.] Arizona State Univ, Sch Engn Matter Transport & Energy, Control Syst Engn Lab, Tempe, AZ USA. RP Riley, WT (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM wiriley@mail.nih.gov; cmartinm@asu.edu; daniel.rivera@asu.edu OI Rivera, Daniel/0000-0002-3141-0577 NR 27 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6880 EP 6883 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706212 ER PT S AU Timms, KP Martin, CA Rivera, DE Hekler, EB Riley, W AF Timms, Kevin P. Martin, Cesar A. Rivera, Daniel E. Hekler, Eric B. Riley, William GP IEEE TI Leveraging Intensive Longitudinal Data to Better Understand Health Behaviors SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc AB Behavioral scientists have historically relied on static modeling methodologies. The rise in mobile and wearable sensors has made intensive longitudinal data (ILD)-behavioral data measured frequently over time-increasingly available. Consequently, analytical frameworks are emerging that seek to reliably quantify dynamics reflected in these data. Employing an input-output perspective, dynamical systems models from engineering can characterize time-varying behaviors as processes of change. Specifically, ILD and parameter estimation routines from system identification can be leveraged together to offer parsimonious and quantitative descriptions of dynamic behavioral constructs. The utility of this approach for facilitating a better understanding of health behaviors is illustrated with two examples. In the first example, dynamical systems models are developed for Social Cognitive Theory (SCT), a prominent concept in behavioral science that considers interrelationships between personal factors, the environment, and behaviors. Estimated models are then obtained that explore the role of SCT in a physical activity intervention. The second example uses ILD to model day-to-day changes in smoking levels as a craving-mediated process of behavior change. C1 [Timms, Kevin P.; Martin, Cesar A.; Rivera, Daniel E.] Arizona State Univ, Sch Engn Matter Transport & Energy, Control Syst Engn Lab, Tempe, AZ 85281 USA. [Hekler, Eric B.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA. [Riley, William] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Timms, KP (reprint author), Arizona State Univ, Sch Engn Matter Transport & Energy, Control Syst Engn Lab, Tempe, AZ 85281 USA. EM ktimms@asu.edu; cmartinm@asu.edu; daniel.rivera@asu.edu; eric.hekler@asu.edu; william.riley@nih.gov OI Rivera, Daniel/0000-0002-3141-0577 NR 13 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6888 EP 6891 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706214 ER PT S AU Pierson, TC Diamond, MS AF Pierson, Theodore C. Diamond, Michael S. BE Enquist, LW TI Vaccine Development as a Means to Control Dengue Virus Pathogenesis: Do We Know Enough? SO ANNUAL REVIEW OF VIROLOGY, VOL 1 SE Annual Review of Virology LA English DT Article; Book Chapter DE flavivirus; pathogenesis; humoral immunity; cellular immunity; antibody; neutralization ID WEST-NILE-VIRUS; ANTIBODY-DEPENDENT ENHANCEMENT; NONSTRUCTURAL PROTEIN NS1; FC-GAMMA-RECEPTOR; LIVED PLASMA-CELLS; CD8(+) T-CELLS; MEMORY B-CELLS; CROSS-REACTIVE ANTIBODIES; TICK-BORNE ENCEPHALITIS; ORIGINAL ANTIGENIC SIN AB Dengue virus (DENV) is a mosquito-transmitted RNA virus responsible for 390 million infections each year and significant morbidity and mortality throughout tropical and subtropical regions of the world. Efforts to develop a DENV vaccine span 70 years and include the work of luminaries of the virus vaccine field. Although vaccines have been used to reduce the global health burden of other flaviviruses, the unique requirement for a single vaccine to protect against four different groups of dengue viruses, and the link between secondary infections and DENV disease pathogenesis, has limited success to date. In this review, we discuss several promising DENV vaccine candidates in clinical trials and assess how recent advances in understanding of DENV biology and immunity may expedite efforts toward the development of safe and effective vaccines. C1 [Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA. RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov; diamond@borcim.wustl.edu NR 151 TC 6 Z9 6 U1 1 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2327-056X J9 ANN REV VIROL PY 2014 VL 1 BP 375 EP 398 DI 10.1146/annurev-virology-031413-085453 PG 24 WC Virology SC Virology GA BC2CK UT WOS:000350745100019 PM 26958727 ER PT S AU Risco, C de Castro, IF Sanz-Sanchez, L Narayan, K Grandinetti, G Subramaniam, S AF Risco, Cristina Fernandez de Castro, Isabel Sanz-Sanchez, Laura Narayan, Kedar Grandinetti, Giovanna Subramaniam, Sriram BE Enquist, LW TI Three-Dimensional Imaging of Viral Infections SO ANNUAL REVIEW OF VIROLOGY, VOL 1 SE Annual Review of Virology LA English DT Article; Book Chapter DE 3D electron microscopy; virus-cell interactions; virus entry; virus factory; virus replication; virus egress ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS; SEMLIKI-FOREST-VIRUS; TRANSMISSION ELECTRON-MICROSCOPY; VESICULAR STOMATITIS-VIRUS; TO-CELL TRANSMISSION; BIOLOGY IN-SITU; VACCINIA VIRUS; CRYOELECTRON TOMOGRAPHY; VIROLOGICAL SYNAPSE AB Three-dimensional (3D) imaging technologies are beginning to have significant impact in the field of virology, as they are helping us understand how viruses take control of cells. In this article we review several methodologies for 3D imaging of cells and show how these technologies are contributing to the study of viral infections and the characterization of specialized structures formed in virus-infected cells. We include 3D reconstruction by transmission electron microscopy (TEM) using serial sections, electron tomography, and focused ion beam scanning electron microscopy (FIB-SEM). We summarize from these methods selected contributions to our understanding of viral entry, replication, morphogenesis, egress and propagation, and changes in the spatial architecture of virus-infected cells. In combination with live-cell imaging, correlative microscopy, and new techniques for molecular mapping in situ, the availability of these methods for 3D imaging is expected to provide deeper insights into understanding the structural and dynamic aspects of viral infection. C1 [Risco, Cristina; Fernandez de Castro, Isabel; Sanz-Sanchez, Laura] CSIC, CNB, Cell Struct Lab, Madrid 28049, Spain. [Narayan, Kedar; Grandinetti, Giovanna; Subramaniam, Sriram] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Risco, C (reprint author), CSIC, CNB, Cell Struct Lab, Madrid 28049, Spain. EM crisco@cnb.csic.es; subramas@mail.nih.gov NR 150 TC 11 Z9 11 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2327-056X J9 ANN REV VIROL PY 2014 VL 1 BP 453 EP + DI 10.1146/annurev-virology-031413-085351 PG 26 WC Virology SC Virology GA BC2CK UT WOS:000350745100022 PM 26958730 ER PT B AU Takebe, N Harris, PJ Kondo, Y Nair, A Ivy, SP Saya, H AF Takebe, Naoko Harris, Pamela jo Kondo, Yutaka Nair, Abhilasha Ivy, S. Percy Saya, Hideyuki BE Rajasekhar, VK TI Targeting Cancer Stem Cells-Modulating Embryonic Stem Cell Signaling, Epigenetics, and Tumor Metabolism SO CANCER STEM CELLS LA English DT Article; Book Chapter ID POLYCOMB-REPRESSIVE COMPLEX; SMALL-MOLECULE ANTAGONISTS; SELECTIVELY INDUCES APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; METHYLTRANSFERASE GENE EZH2; GAMMA-SECRETASE INHIBITORS; TO-MESENCHYMAL TRANSITION; HEDGEHOG PATHWAY; BREAST-CANCER; IN-VIVO C1 [Takebe, Naoko; Harris, Pamela jo; Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Rockville, MD 20850 USA. [Kondo, Yutaka] Aichi Canc Ctr, Res Inst, Div Epigen, Chikusa Ku, Nagoya, Aichi 464, Japan. [Nair, Abhilasha] NCI, Div Canc Treatment & Diag, NIH, Rockville, MD USA. [Saya, Hideyuki] Keio Univ, Sch Med, Div Gene Regulat, Inst Adv Med Res,Shinjuku Ku, Tokyo, Japan. RP Takebe, N (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Rockville, MD 20850 USA. NR 158 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-35620-3; 978-1-118-35616-6 PY 2014 BP 297 EP 317 D2 10.1002/9781118356203 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BC3IM UT WOS:000351670400025 ER PT B AU Karasawa, H Castro, NP Rangel, MC Salomon, DS AF Karasawa, Hideaki Castro, Nadia P. Rangel, Maria Cristina Salomon, David S. BE Rajasekhar, VK TI The Role of Cripto-1 in Cancer and Cancer Stem Cells SO CANCER STEM CELLS LA English DT Article; Book Chapter ID ACUTE MYELOID-LEUKEMIA; CARCINOMA-CELLS; TRANSGENIC MICE; ANTISENSE OLIGONUCLEOTIDES; GENE-EXPRESSION; MAMMARY-GLAND; MESENCHYMAL TRANSITION; TUMOR PROGRESSION; INITIATING CELLS; EPITHELIAL-CELLS C1 [Karasawa, Hideaki; Castro, Nadia P.; Rangel, Maria Cristina; Salomon, David S.] Frederick Natl Lab Canc Res, Tumor Growth Factor Sect, Lab Canc Prevent, Frederick, MD 21701 USA. RP Karasawa, H (reprint author), Frederick Natl Lab Canc Res, Tumor Growth Factor Sect, Lab Canc Prevent, Frederick, MD 21701 USA. NR 75 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-35620-3; 978-1-118-35616-6 PY 2014 BP 331 EP 345 D2 10.1002/9781118356203 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BC3IM UT WOS:000351670400027 ER PT J AU Mendy, M Caboux, E Sylla, BS Dillner, J Chinquee, J Wild, C AF Mendy, Maimuna Caboux, Elodie Sylla, Bakary S. Dillner, Joakim Chinquee, Joseph Wild, Christopher CA BCNet Survey Participants TI Infrastructure and Facilities for Human Biobanking in Low- and Middle-Income Countries: A Situation Analysis SO PATHOBIOLOGY LA English DT Article DE Biobank; Low- and middle-income countries; Biobank and Cohort Building; Ethical, legal, and social issues ID HUMAN-PAPILLOMAVIRUS; CANCER; AFRICA; COHORT; RISK; POPULATIONS; MORTALITY AB Objective: To collect information on biobanking facilities in low-and middle-income countries (LMICs) as a first step towards establishing an LMIC biobank and cohort building network (BCNet) to support research, with a focus on cancer control. Method: Sixty centres were identified from sources including cancer centres, universities, hospitals, and public health facilities and invited to participate in a survey between December 2012 and March 2013. Results: Of the 27 centres (45%) that responded, most have existed for < 10 years. They store between 1,000 and 1,000,000 research samples as well as samples remaining after clinical diagnosis. Sample storage is mostly in freezers, although 45% (9/20) of the centres do not have regular access to electricity. Biobank managers, sample management systems, and mechanisms for follow-up using linkages are uncommon. Many (80%; 21/26) of the centres have regulations to govern research, but regulations for the use of biobank resources (samples and data) are not well developed. Conclusions: Biobanking facilities are being developed in LMICs. Shortcomings in international visibility, sample sharing regulations, standardization, quality assurance, and sample management systems could be alleviated by international networking. Stakeholders need to work together to increase access to high-quality biological resources for scientific research. (C) 2015 S. Karger AG, Basel C1 [Mendy, Maimuna; Caboux, Elodie; Sylla, Bakary S.; Wild, Christopher] Int Agcy Res Canc, FR-69372 Lyon 8, France. [Dillner, Joakim] Karolinska Inst, Biobanking & Mol Resource Infrastruct Sweden, Stockholm, Sweden. [Chinquee, Joseph] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. RP Mendy, M (reprint author), Int Agcy Res Canc, Lab Serv, 150 Cours Albert Thomas, FR-69372 Lyon 8, France. EM mendym@iarc.fr OI Babb de Villiers, Chantal/0000-0003-1334-1819 FU IARC; USA NCI/CGH FX The authors would like to thank IARC and USA NCI/CGH for providing funding for the study, Abdullaev Zied (NIH/NCI) for assistance in the data analysis, and the colleagues of BCNet members and their respective centres who participated in the survey. NR 30 TC 4 Z9 4 U1 3 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 EI 1423-0291 J9 PATHOBIOLOGY JI Pathobiology PY 2014 VL 81 IS 5-6 BP 252 EP 260 DI 10.1159/000362093 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CE0VY UT WOS:000351528500005 PM 25792214 ER PT J AU Yu, PY Han, WX Villar, VAM Yang, Y Lu, QS Lee, HW Li, FM Quinn, MT Gildea, JJ Felder, RA Jose, PA AF Yu, Peiying Han, Weixing Villar, Van Anthony M. Yang, Yu Lu, Quansheng Lee, Hewang Li, Fengmin Quinn, Mark T. Gildea, John J. Felder, Robin A. Jose, Pedro A. TI Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells SO REDOX BIOLOGY LA English DT Article DE NOX5; ROS; Oxidative stress; Dopamine receptor ID VASCULAR SMOOTH-MUSCLE; REACTIVE OXYGEN; NAD(P)H OXIDASE; RECEPTOR HYPERPHOSPHORYLATION; ESSENTIAL-HYPERTENSION; CL-/HCO3-EXCHANGER; D-1-LIKE RECEPTORS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; PROTEIN-KINASE AB NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2 +/- 0.7-fold, 5.2 +/- 0.7-fold, and 2.8 +/- 0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5 +/- 0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2 +/- 0.2-fold greater in HT than NT (P= < 0.001, n=6-14/group). lonomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n =4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenyleneiodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (-45.1 +/- 3.2% vs. mock-siRNA, n=6-8) in HT. D-1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT ( -32.5 +/- 1.8%) than HT (-14.8 +/- 1.8). In contrast to the marked increase in expression and activity of NOX5 in HT. NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Yu, Peiying; Villar, Van Anthony M.; Yang, Yu; Lee, Hewang; Jose, Pedro A.] Univ Maryland, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21201 USA. [Han, Weixing] Anhui Med Univ, Dept Cardiovasc Med, Affiliated Hosp 1, Hefei, Anhui, Peoples R China. [Lu, Quansheng] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Li, Fengmin] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Quinn, Mark T.] Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA. [Gildea, John J.; Felder, Robin A.] Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA. [Jose, Pedro A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Jose, PA (reprint author), Univ Maryland, Sch Med, Div Nephrol, Dept Med, 20 Penn St,Suite S003C, Baltimore, MD 21201 USA. EM pjose@medicine.umaryland.edu FU National Institutes of Health [HL023081, HL074940, DK039308, HL092196, HL068686, GM 103500] FX These studies were supported in part by grants from the National Institutes of Health (HL023081, HL074940, DK039308, HL092196, HL068686, and GM 103500). NR 47 TC 12 Z9 12 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2014 VL 2 BP 570 EP 579 DI 10.1016/j.redox.2014.01.020 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CD0MY UT WOS:000350769600066 PM 24688893 ER PT J AU Song, BJ Akbar, M Abdelmegeed, MA Byun, K Lee, B Yoon, SK Hardwick, JP AF Song, Byoung-Joon Akbar, Mohammed Abdelmegeed, Mohamed A. Byun, Kyunghee Lee, Bonghee Yoon, Seung Kew Hardwick, James P. TI Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications SO REDOX BIOLOGY LA English DT Article DE Nitroxidative stress; Redox; Post-translational modifications; Mitochondrial proteins; Mitochondrial dysfunction; Tissue injury ID INDUCED LIVER-INJURY; NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; HEPATIC ISCHEMIA-REPERFUSION; TARGETED ANTIOXIDANT MITOQ; NITRIC-OXIDE SYNTHASE; CYTOCHROME-C-OXIDASE; OXIDATIVE STRESS; TERMINAL KINASE; RAT-LIVER; CELL-DEATH AB Mitochondria are critically important in providing cellular energy ATP as well as their involvement in anfi-oxiclant defense, fat oxidation, intermediary metabolism and cell death processes lt is well-established that mitochondrial functions are suppressed when living cells or organisms are exposed to potentially toxic agents including alcohol, high fat diets, smoking and certain drugs or in many pathophysiological states through increased levels of oxidative/nitrative stress. Under elevated nitroxidative stress, cellular macromolecules proteins, DNA, and lipids can undergo different oxidative modifications, leading to disruption of their normal, sometimes critical, physiological functions. Recent reports also indicated that many mitochondrial proteins are modified via various post-translation modifications (PTMs) and primarily inactivated. Because of the recently-emerging information, in this review, we specifically focus on the mechanisms and roles of five major PTMs (namely oxidation, nitration, phosphorylation, acetylation, and adduct formation with lipid-peroxides, reactive metabolites, or advanced glycation end products) in experimental models of alcoholic and nonalcoholic fatty liver disease as well as acute hepatic injury caused by toxic compounds. We also highlight the role of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) in some of these PTM changes. Finally, we discuss translational research opportunities with natural and/or synthetic anti-oxidants, which can prevent or delay the onset of mitochondial dysfunction, fat accumulation and tissue injury. Published by Elsevier B.V. C1 [Song, Byoung-Joon; Akbar, Mohammed; Abdelmegeed, Mohamed A.] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Byun, Kyunghee; Lee, Bonghee] Gachon Univ, Sch Med, Lee Gil Ya Canc & Diabet Inst, Ctr Genom & Prote, Inchon, South Korea. [Yoon, Seung Kew] Catholic Univ, Coll Med, Liver Res Ctr, Seoul, South Korea. [Hardwick, James P.] Northeast Ohio Med Univ, Dept Integrat Med Sci, Biochem & Mol Pathol, Rootstown, OH USA. RP Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bj.song@nih.gov FU Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism. The authors thank Dr. Klaus Gawrisch for his support. The authors do not have any conflict of interest. NR 242 TC 17 Z9 19 U1 4 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2014 VL 3 BP 109 EP 123 DI 10.1016/j.redox.2014.10.004 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CD1CW UT WOS:000350812500014 PM 25465468 ER PT S AU Chan, CC Ardeljan, D AF Chan, Chi-Chao Ardeljan, Daniel BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Molecular Pathology of Macrophages and Interleukin-17 in Age-Related Macular Degeneration SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Age-related macular degeneration; Macrophage; IL-17; Inflammation; Eye ID BRUCHS MEMBRANE; T-CELLS; POLARIZATION; IL-17; INFLAMMATION; ACTIVATION; PLASTICITY; FEATURES; DISEASE; NLRP3 AB The pathology of age-related macular degeneration (AMD) is characterized by degeneration of photoreceptors and retinal pigment epithelial cells as well as by changes of choroidal capillaries in the macula. Although AMD is not a typical uveitis, there is a consistence and an imbalance of ocular para-inflammation. Ocular inflammation, particularly in the macula, plays a critical role in AMD pathogenesis. The inflammatory and immune-related elements involved in AMD include inflammatory and related cells as well as the secreted molecules and factors from these cells. Innate immune system elements such as macrophages and cytokines play an important role in AMD pathology and pathogenesis. This chapter reviews the observed deviation in macrophage plasticity and the elevated expression of interleukin-17 in AMD eyes while discussing potential contributions to AMD pathogenesis. Targeting of these specific inflammatory pathways and mole-cules at appropriate times should be explored and may become promising novel adjunct agents to AMD therapy. C1 [Chan, Chi-Chao; Ardeljan, Daniel] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov; ardeljand@mail.nih.gov FU Intramural NIH HHS [ZIA EY000222-28, ZIA EY000418-10] NR 31 TC 12 Z9 14 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 193 EP 198 DI 10.1007/978-1-4614-3209-8_25 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200026 PM 24664698 ER PT S AU Wang, MH Wong, WT AF Wang, Minhua Wong, Wai T. BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Microglia-Muller Cell Interactions in the Retina SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Muller cells; Microglia; Inflammation; Retina; Gliosis ID CENTRAL-NERVOUS-SYSTEM; IN-VIVO; NEURONAL-ACTIVITY; GLIAL-CELLS; BRAIN; ACTIVATION; RELEASE; ATP; HEMICHANNELS; INFLAMMATION AB Microglia and Muller cells are cell types that feature prominently in responses to disease and injury in the retina. However, their mutual interactions have not been investigated in detail. Here, we review evidence that indicate that these two cell populations exchange functionally significant signals under uninjured conditions and during retinal inflammation. Under normal conditions, Muller cells constitute a potential source of extracellular ATP that mediates the activitydependent regulation of microglial dynamic process motility. Following microglial activation in inflammation, microglia can signal to Muller cells, influencing their morphological, molecular, and functional responses. Microglia-Muller cell interactions appear to be a mode of bi-directional communications that help shape the overall injury response in the retina. C1 [Wang, Minhua; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, 6 Ctr Dr 6-215, Bethesda, MD 20892 USA. EM minhua.wang@nih.gov; wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS [ZIA EY000463-07] NR 37 TC 16 Z9 17 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 333 EP 338 DI 10.1007/978-1-4614-3209-8_42 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200043 PM 24664715 ER PT S AU Hao, H Gregorski, J Qian, HH Li, YC Gao, CY Idrees, S Zhang, B AF Hao, Hong Gregorski, Janina Qian, Haohua Li, Yichao Gao, Chun Y. Idrees, Sana Zhang, Bin BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI In Vivo Function of the ER-Golgi Transport Protein LMAN1 in Photoreceptor Homeostasis SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE LMAN1; NRL; Photoreceptor; Transport; Homeostasis ID COMPLEX; GM130 AB LMAN1 is a type I transmembrane protein that selectively transports its cargo proteins from ER to ER-Golgi intermediate compartment (ERGIC) and Golgi. Lman1 is a direct target of the transcription factor NRL in mouse retina. Therefore, we examined the in vivo function of LMAN1 in retina. Although Lman1(-/-) mouse eyes did not show abnormality in histology and electroretinogram analysis at 3 months, Lman1(-/-) retina at 6 months showed a decrease in cis-Golgi markers GM130 and GRASP65. We also observed abnormal level and location of Rhodopsin in these mice. Taken together, LMAN1 may play a role in photoreceptor gene transport and homeostasis. C1 [Hao, Hong] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Gregorski, Janina] New York Med Coll, Grad Sch Basic Med Sci, Valhalla, NY 10595 USA. [Qian, Haohua; Li, Yichao] NEI, Visual Funct Core, Bethesda, MD 20892 USA. [Gao, Chun Y.] NEI, Biol Imaging Core Facil, Bethesda, MD 20892 USA. [Idrees, Sana] George Washington Univ, Sch Med, Washington, DC 20037 USA. [Zhang, Bin] Cleveland Clin Fdn, Lerner Res Inst, Genom Med Inst, Cleveland, OH 44195 USA. RP Hao, H (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, MSC0610,6 Ctr Dr, Bethesda, MD 20892 USA. EM haoh@mail.nih.gov; janina_gregorski@nymc.edu; haohua.qian@nih.gov; Yichao.li@nih.gov; sidrees@gwmail.gwu.edu; zhangb@ccf.org FU Intramural Programs of the National Eye Institute FX We thank Dr. Anand Swaroop for advice and support. We also thank N-NRL members for technical assistance. This study was supported by Intramural Programs of the National Eye Institute. NR 10 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 395 EP 399 DI 10.1007/978-1-4614-3209-8_50 PG 5 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200051 PM 24664723 ER PT S AU Egwuagu, CE AF Egwuagu, Charles E. BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Uveitis; Retinal degeneration; Insulin resistance; Interferon-gamma; Cytokines; Suppressor of cytokine signaling; Experimental autoimmune uveitis; EAU ID DIABETIC-RETINOPATHY; UVEITIS; CELLS; MECHANISMS AB Elevated levels of inflammatory cytokines in the vitreous of patients with chronic intraocular inflammatory (uveitis) have long been suspected to contribute to the pathogenesis of retinal degenerative diseases. However, direct connection between chronic inflammation and development of retinal degenerative diseases has been difficult to establish because we lack an appropriate animal model of co-existing chronic intraocular inflammation and neurodegeneration. This report discusses new developments in immunological and diabetic research that suggest that persistent secretion of pro-inflammatory cytokines during uveitis might induce insulin resistance and retinal degenerative changes that contribute to the pathogenesis of Diabetic Retinopathy (DR), a retinal dystrophy of significant public health importance. C1 NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 12 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 417 EP 425 DI 10.1007/978-1-4614-3209-8_53 PG 9 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200054 PM 24664726 ER PT S AU Ziccardi, L Vijayasarathy, C Bush, RA Sieving, PA AF Ziccardi, Lucia Vijayasarathy, Camasamudram Bush, Ronald A. Sieving, Paul A. BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Photoreceptor Pathology in the X-Linked Retinoschisis (XLRS) Mouse Results in Delayed Rod Maturation and Impaired Light Driven Transducin Translocation SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Transducin; Arrestin; Translocation; Photoreceptors; Retinoschisis ID PROTEIN; DEGENERATION; MICE AB Light-activated movement of transducin-alpha (G(alpha t1)) from rod photoreceptor outer segments (ROS) into inner segments (IS) enables rods to rapidly adapt to changes in light intensity. The threshold light intensity at which G(alpha t1) translocates from ROS into IS is primarily determined by the rates of activation and inactivation of G(alpha t1). Loss-of-expression of the retina specific cell surface protein, retinoschsin (Rs1-KO), led to a dramatic 3-10 fold increase, depending on age, in the luminance threshold for transducin translocation from ROS into IS compared with wild-type control. In contrast, arrestin translocated from IS into ROS at the same light intensity both in WT and Rs1-KO mice. Biochemical changes, including reduced transducin protein levels and enhanced transducin GTPase activity, explain the shift in light intensity threshold for G(alpha t1) translocation in Rs1-KO mice. These changes in Rs1-KO mice were also associated with age related alterations in photoreceptor morphology and transcription factor expression that suggest delayed photoreceptor maturation. C1 [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Ziccardi, Lucia] GB Bietti Fdn, IRCCS, Ist Ricovero & Cura Carattere Sci, I-00198 Rome, Italy. [Vijayasarathy, Camasamudram; Bush, Ronald A.] Natl Inst Deafness & Other Commun Disorders, STRRMD, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Room 6A03, Bethesda, MD 20892 USA. EM luxzic@hotmail.com; camasamv@nidcd.nih.gov; bushr@nidcd.nih.gov; paulsieving@nei.nih.gov FU National Institutes of Health, National Institute on Deafness and Other Communication Disorders; National Institutes of Health, National Eye Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute on Deafness and Other Communication Disorders, and the National Eye Institute. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 559 EP 566 DI 10.1007/978-1-4614-3209-8_71 PG 8 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200072 PM 24664744 ER PT S AU Bonilha, VL Rayborn, ME Yang, XP Xie, CS Cai, HB AF Bonilha, Vera L. Rayborn, Mary E. Yang, Xiaoping Xie, Chengsong Cai, Huaibin BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Oxidative Stress Regulation by DJ-1 in the Retinal Pigment Epithelium SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Retinal pigment epithelium; Oxidative stress; Reactive oxygen species; DJ-1; Histology ID CYSTEINE-SULFINIC ACID; MITOCHONDRIAL LOCALIZATION; PARKINSONS-DISEASE; ESCHERICHIA-COLI; DROSOPHILA DJ-1; PROTEIN DJ-1; CELL-DEATH; GENE; INACTIVATION; LEADS AB DJ-1 is a protein expressed in many tissues including the brain where it has been extensively studied due to its association with Parkinson's Disease (PD). DJ-1 was reported to function as an antioxidant, redox-sensitive molecular chaperone, and transcription regulator, which protected cells from oxidative stress by modifying signaling pathways that regulate cell survival. Here we discuss our progress toward characterization of the DJ-1 function in the protection of RPE to oxidative stress. C1 [Bonilha, Vera L.; Rayborn, Mary E.; Yang, Xiaoping] Cleveland Clin, Cole Eye Inst, Dept Ophthalmol, Lerner Coll Med, Cleveland, OH 44195 USA. [Xie, Chengsong; Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Bonilha, VL (reprint author), Cleveland Clin, Cole Eye Inst, Dept Ophthalmol, Lerner Coll Med, I31,9500 Euclid Ave, Cleveland, OH 44195 USA. EM bonilhav@ccf.org; rayborm@ccf.org; YANGX@ccf.org; xiech@mail.nih.gov; caih@mail.nih.gov FU Foundation Fighting Blindness; Research to Prevent Blindness; Cleveland Clinic Foundation; intramural research program of National Institute on Aging FX Supported by Research Center grants from the Foundation Fighting Blindness and Research to Prevent Blindness and funds from the Cleveland Clinic Foundation and partially by the intramural research program of National Institute on Aging (HC). NR 23 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 649 EP 654 DI 10.1007/978-1-4614-3209-8_81 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200082 PM 24664754 ER PT S AU Fuller, JA Shaw, GC Bonnet-Wersinger, D Hansen, BS Berlinicke, CA Inglese, J Zack, DJ AF Fuller, John A. Shaw, Gillian C. Bonnet-Wersinger, Delphine Hansen, Baranda S. Berlinicke, Cynthia A. Inglese, James Zack, Donald J. BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI A High Content Screening Approach to Identify Molecules Neuroprotective for Photoreceptor Cells SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Neuroprotection; Photoreceptor; HTS; Screening; High content analysis ID ENDOPLASMIC-RETICULUM STRESS; RETINAL DEGENERATION; GENE-THERAPY; CONGENITAL AMAUROSIS; RETINITIS-PIGMENTOSA; OXIDATIVE STRESS; NADPH OXIDASE; MOUSE MODELS; PARAQUAT; DEATH AB Purpose Retinal degenerations are a heterogeneous group of diseases in which there is slow but progressive loss of photoreceptors (PR). There are currently no approved therapies for treating retinal degenerations. In an effort to identify novel small molecules that are (1) neuroprotective and (2) promote PR differentiation, we have developed microscale (1,536 well) cell culture assays using primary retinal neurons. Methods Primary murine retinal cells are isolated, seeded, treated with a 1,280 compound chemical library in a 7 point titration and then cultured under conditions developed to assay protection against an introduced stress or enhance PR differentiation. In the protection assays a chemical insult is introduced and viability assessed after 72 h using CellTiterGlo, a single-step chemiluminescent reagent. In the differentiation assay, cells are isolated from the rhodopsin-GFP knock-in mouse and PR differentiation is assessed by fixing cells after 21 days in culture and imaging with the Acumen plate-based laser cytometer (TTP Labtech) to determine number and intensity of GFP-expressing cells. Positive wells are re-imaged at higher resolution with an INCell2000 automated microscope (GE). Concentration-response curves are generated to pharmacologically profile each compound and hits identified by xx. Results We have developed PR differentiation and neuroprotection assays with a signal to background (S/B) ratios of 11 and 3, and a coefficient of variation (CV) of 20 and 9 %, suitable for chemical screening. Staurosporine has been shown in our differentiation assay to simultaneously increase the number of rhodopsin positive objects while decreasing the mean rhodopsin intensity and punctate rhodopsin fluorescent objects. Conclusions Using primary murine retinal cells, we developed high throughput assays to identify small molecules that influence PR development and survival. By screening multiple compound concentrations, dose-response curves can be generated, and the false negative rate minimized. It is hoped that this work will identify both potential preclinical candidates as well as molecular probes that will be useful for analysis of the molecular mechanisms that promote PR differentiation and survival. C1 [Fuller, John A.; Shaw, Gillian C.; Bonnet-Wersinger, Delphine; Hansen, Baranda S.; Berlinicke, Cynthia A.; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21231 USA. [Inglese, James] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Inglese, James] Natl Human Genome Inst, NIH, Bethesda, MD USA. [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Dept Neurosci, Baltimore, MD USA. [Zack, Donald J.] Inst Vis, F-75012 Paris, France. RP Fuller, JA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 400 N Broadway, Baltimore, MD 21231 USA. EM jfulle19@jhmi.edu; gshaw6@jhmi.edu; delphine.bonnet@inserm.fr; bhansen2@jhmi.edu; jinglese@mail.nih.gov; dzack@jhmi.edu OI Fuller, John/0000-0002-6587-146X; Zack, Don/0000-0002-7966-1973 FU FFB/Wynn-Gund Translational Research Acceleration Program Award FX We thank John Wilson and Ted Wensel (Baylor College of Medicine) for generously providing Rho-GFP mice, and Patricia Dranchak, Sam Hasson, and Ryan MacArthur of the NIH NCATS DPI for their help and assistance. This work was funded by an FFB/Wynn-Gund Translational Research Acceleration Program Award. NR 27 TC 4 Z9 4 U1 2 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 773 EP 781 DI 10.1007/978-1-4614-3209-8_97 PG 9 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200098 PM 24664770 ER PT S AU Rapp, M Woo, G Al-Ubaidi, MR Becerra, SP Subramanian, P AF Rapp, Matthew Woo, Grace Al-Ubaidi, Muayyad R. Becerra, S. Patricia Subramanian, Preeti BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Pigment Epithelium-Derived Factor Protects Cone Photoreceptor-Derived 661W Cells from Light Damage Through Akt Activation SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE PEDF; PEDF-R; Photoreceptor; 661W cells; Akt phosphorylation; Survival ID FACTOR PEDF; INTERPHOTORECEPTOR MATRIX; GENE-TRANSFER; GROWTH; ANGIOGENESIS; INJURY; NEOVASCULARIZATION; IDENTIFICATION; EXPRESSION; RECEPTOR AB Pigment epithelium-derived factor (PEDF) can delay and prevent the death of photoreceptors in vivo. We investigated the survival activity of PEDF on cone photoreceptor-derived 661W cells in culture, the presence of PEDF receptor (PEDF-R) in these cells and the activation of prosurvival Akt. Cell death was induced by light exposure in the presence of 9-cis retinal. Cell viability assays showed that PEDF increased the number of 661W cells exposed to these conditions. Western blots showed that PEDF-treated 661W cells had a higher ratio of phosphorylated Akt to total Akt than untreated cells. The PEDF receptor PEDF-R was immunodetected in the plasma membrane fractions of 661W cells. The results demonstrated that PEDF can protect 661W cells against light-induced cell death and suggest that the binding of PEDF to cell surface PEDF-R triggers a prosurvival signaling pathway. C1 [Rapp, Matthew; Woo, Grace; Becerra, S. Patricia; Subramanian, Preeti] NEI, NIH, Bethesda, MD 20892 USA. [Al-Ubaidi, Muayyad R.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA. [Al-Ubaidi, Muayyad R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK 73104 USA. RP Subramanian, P (reprint author), NEI, NIH, Bldg 6,Rm 131F,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA. EM rappm1@umbc.edu; gracebeewoo@gmail.com; muayyad-al-ubaidi@ouhsc.edu; becerrap@nei.nih.gov; subramanianp@nei.nih.gov NR 29 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 813 EP 820 DI 10.1007/978-1-4614-3209-8_102 PG 8 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200103 PM 24664775 ER PT S AU Qasba, P AF Qasba, Pankaj BE Corey, SJ Kimmel, M Leonard, JN TI A Systems Approach to Blood Disorders SO SYSTEMS BIOLOGY APPROACH TO BLOOD SE Advances in Experimental Medicine and Biology LA English DT Editorial Material; Book Chapter DE Hematopoiesis; Regulatory networks; Blood system; Erythropoiesis; Fanconi anemia (FA); Diamond-Blackfan anemia (DBA); Bone marrow failure syndromes (BMFs); In silco; System biology; System medicine; Omics; Multiscale; Microfluidics; Hemoglobinopathies; Fetal hemoglobin; Induced pluripotent stem (iPS) cells ID DIAMOND-BLACKFAN ANEMIA; SICKLE-CELL-ANEMIA; STEM-CELLS; DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; LINEAGE FATE; MUTATIONS; SPECIFICATION; BIOLOGY AB A systems approach to blood diseases can help make essential contributions to our ability to diagnose, treat, and perhaps even prevent common diseases in humans. Using blood as a window, one can study health and disease through this unique tool box with reactive biological fluids that mirrors the prevailing hemodynamics of the vessel walls and the various blood cell types. Many blood diseases, rare and common, can and have been exploited using systems biology approaches with successful results and therefore ideal models for systems medicine. More importantly, hematopoiesis offers one of the best studied systems with insight into stem cell biology, cellular interaction, development; linage programming and reprogramming that are influenced every day by the most mature and understood regulatory networks. C1 NHLBI, Blood Dis Branch, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP Qasba, P (reprint author), NHLBI, Blood Dis Branch, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA. EM qasbap@nhlbi.nih.gov NR 33 TC 0 Z9 0 U1 3 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-2095-2; 978-1-4939-2094-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 844 BP 395 EP 399 DI 10.1007/978-1-4939-2095-2_19 D2 10.1007/978-1-4939-2095-2 PG 5 WC Biology; Hematology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Hematology; Research & Experimental Medicine GA BC1SY UT WOS:000350414400022 PM 25480652 ER PT S AU Soemedi, R Vega, H Belmont, JM Ramachandran, S Fairbrother, WG AF Soemedi, Rachel Vega, Hugo Belmont, Judson M. Ramachandran, Sohini Fairbrother, William G. BE Yeo, GW TI Genetic Variation and RNA Binding Proteins: Tools and Techniques to Detect Functional Polymorphisms SO SYSTEMS BIOLOGY OF RNA BINDING PROTEINS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Pre-mRNA splicing; Human genetic variation; Single nucleotide polymorphism (SNP); RNA binding protein; Polypyrimidine track binding protein (PTB) ID PRE-MESSENGER-RNA; EXONIC SPLICING ENHANCERS; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME SEQUENCE VARIATION; CONTEXT-FREE GRAMMARS; HUMAN-DISEASE GENES; IN-VIVO; SECONDARY STRUCTURE; SR PROTEINS; COMPUTATIONAL TOOLS AB At its most fundamental level the goal of genetics is to connect genotype to phenotype. This question is asked at a basic level evaluating the role of genes and pathways in genetic model organism. Increasingly, this question is being asked in the clinic. Genomes of individuals and populations are being sequenced and compared. The challenge often comes at the stage of analysis. The variant positions are analyzed with the hope of understanding human disease. However after a genome or exome has been sequenced, the researcher is often deluged with hundreds of potentially relevant variations. Traditionally, amino-acid changing mutations were considered the tractable class of disease-causing mutations; however, mutations that disrupt noncoding elements are the subject of growing interest. These noncoding changes are a major avenue of disease (e.g., one in three hereditary disease alleles are predicted to affect splicing). Here, we review some current practices of medical genetics, the basic theory behind biochemical binding and functional assays, and then explore technical advances in how variations that alter RNA protein recognition events are detected and studied. These advances are advances in scale-high--throughput implementations of traditional biochemical assays that are feasible to perform in any molecular biology laboratory. This chapter utilizes a case study approach to illustrate some methods for analyzing polymorphisms. The first characterizes a functional intronic SNP that deletes a high affinity PTB site using traditional low-throughput biochemical and functional assays. From here we demonstrate the utility of high-throughput splicing and spliceosome assembly assays for screening large sets of SNPs and disease alleles for allelic differences in gene expression. Finally we perform three pilot drug screens with small molecules (G418, tetracycline, and valproic acid) that illustrate how compounds that rescue specific instances of differential pre-mRNA processing can be discovered. C1 [Soemedi, Rachel; Ramachandran, Sohini; Fairbrother, William G.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. [Soemedi, Rachel; Vega, Hugo; Belmont, Judson M.; Fairbrother, William G.] Brown Univ, Mol & Cellular Biol & Biochem, Providence, RI 02912 USA. [Vega, Hugo] NIH, Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA. [Vega, Hugo] NHGRI, Bethesda, MD 20892 USA. [Ramachandran, Sohini] Brown Univ, Ecol & Evolutionary Biol, Providence, RI 02912 USA. [Fairbrother, William G.] Brown Univ, Ctr Biomed Engn, Providence, RI 02912 USA. RP Fairbrother, WG (reprint author), Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. EM William_fairbrother@brown.edu NR 130 TC 4 Z9 4 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-1221-6; 978-1-4939-1220-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 825 BP 227 EP 266 DI 10.1007/978-1-4939-1221-6_7 D2 10.1007/978-1-4939-1221-6 PG 40 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA BC1TR UT WOS:000350418400008 PM 25201108 ER PT J AU Shinohara, RT Sweeney, EM Goldsmith, J Shiee, N Mateen, FJ Calabresi, PA Jarso, S Pham, DL Reich, DS Crainiceanu, CM AF Shinohara, Russell T. Sweeney, Elizabeth M. Goldsmith, Jeff Shiee, Navid Mateen, Farrah J. Calabresi, Peter A. Jarso, Samson Pham, Dzung L. Reich, Daniel S. Crainiceanu, Ciprian M. CA Australian Imaging Biomarkers Life Alzheimers Dis Neuroimaging Initia TI Statistical normalization techniques for magnetic resonance imaging SO NEUROIMAGE-CLINICAL LA English DT Article DE Magnetic resonance imaging; Normalization; Statistics; Image analysis ID MULTIPLE-SCLEROSIS; INTENSITY STANDARDIZATION; ALZHEIMERS-DISEASE; MRI; BRAIN; SCALE; IMAGES AB While computed tomography and other imaging techniques are measured in absolute units with physical meaning, magnetic resonance images are expressed in arbitrary units that are difficult to interpret and differ between study visits and subjects. Much work in the image processing literature on intensity normalization has focused on histogram matching and other histogram mapping techniques, with little emphasis on normalizing images to have biologically interpretable units. Furthermore, there are no formalized principles or goals for the crucial comparability of image intensities within and across subjects. To address this, we propose a set of criteria necessary for the normalization of images. We further propose simple and robust biologically motivated normalization techniques for multisequence brain imaging that have the same interpretation across acquisitions and satisfy the proposed criteria. We compare the performance of different normalization methods in thousands of images of patients with Alzheimer's disease, hundreds of patients with multiple sclerosis, and hundreds of healthy subjects obtained in several different studies at dozens of imaging centers. (C) 2014 Published by Elsevier Inc. C1 [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neurol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Goldsmith, Jeff; Crainiceanu, Ciprian M.] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Jarso, Samson; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. RP Shinohara, RT (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, 210 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rshi@upenn.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke; National Institute of Neurological Disorders and Stroke [R01NS060910, R01NS085211]; National Institute of Biomedical Imaging and Bioengineering [R01EB012547]; Epidemiology and Biostatistics of Aging Training Grant from the National Institute on Aging [T32 AG000247] FX Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimers Association; Alzheimers Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, Rev October 16, 2012 San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.; The authors thank Irene Cortese, Colin Shea, Roger Stone, the NINDS clinical group, and the NIMH/NINDS Functional Magnetic Resonance Imaging Facility technologists, who were instrumental in collecting and processing the data for this study. The research was partially supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. The research of Shinohara and Crainiceanu was supported by Award Numbers R01NS060910 and R01NS085211 from the National Institute of Neurological Disorders and Stroke and Award Number R01EB012547 from the National Institute of Biomedical Imaging and Bioengineering. Shinohara was supported in part by the Epidemiology and Biostatistics of Aging Training Grant T32 AG000247 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 25 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 6 BP 9 EP 19 DI 10.1016/j.nicl.2014.08.008 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CB5LL UT WOS:000349668500002 PM 25379412 ER PT J AU Ning, J Qin, J Shen, Y AF Ning, Jing Qin, Jing Shen, Yu TI SEMIPARAMETRIC ACCELERATED FAILURE TIME MODEL FOR LENGTH-BIASED DATA WITH APPLICATION TO DEMENTIA STUDY SO STATISTICA SINICA LA English DT Article DE Accelerated failure time model; dementia; dependent censoring; estimating equation; length-biased sampling; prevalent cohort ID PSEUDO-PARTIAL LIKELIHOOD; PREVALENT COHORT DATA; RIGHT-CENSORED DATA; LINEAR RANK-TESTS; NONPARAMETRIC-ESTIMATION; REGRESSION-ANALYSIS; SURVIVAL-DATA; ALZHEIMER-DISEASE; TRUNCATED DATA; LARGE-SAMPLE AB A semiparametric accelerated failure time (AFT) model is proposed to evaluate the effects of risk factors on the unbiased failure times for the target population given the observed length-biased data. The analysis of length-biased data is complicated by informative right censoring due to the biased sampling mechanism, and consequently the techniques for conventional survival analysis are not applicable. We propose estimating equation methods for estimation and show the asymptotic properties of the proposed estimators. The small sample performance of the estimating methods are investigated and compared with that of existing methods under various underlying distributions and censoring mechanisms. We apply the proposed model and estimating methods to a prevalent cohort study, the Canadian Study of Health and Aging (CSHA), to evaluate the survival duration according to diagnosis of subtype of dementia. C1 [Ning, Jing; Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD USA. RP Ning, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. EM jning@mdanderson.org; jingqin@niaid.nih.gov; yshen@mdanderson.org OI Shen, Yu/0000-0002-3899-7868 FU National Institutes of Health [CA0769466]; Seniors' Independence Research Program through the National Health Research and Development Program of Health Canada [6606-3954-MC(S)]; Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program; NHRDP [6603-1417-302(R)]; Bayer Incorporated; British Columbia Health Research Foundation [38 (93-2), 34 (96-1)] FX This work was supported in part by grant CA0769466 from the National Institutes of Health. The authors are grateful to Professor M. Asgharian and investigators from the Canadian Study of Health and Aging for providing us with the dementia data collected as part of the CSHA. The core study was funded by the Seniors' Independence Research Program through the National Health Research and Development Program of Health Canada (Project no.6606-3954-MC(S)). Additional funding was provided by Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program, NHRDP Project 6603-1417-302(R), Bayer Incorporated, and the British Columbia Health Research Foundation Projects 38 (93-2) and 34 (96-1). The study was coordinated through the University of Ottawa and the Division of Aging and Seniors, Health Canada. NR 47 TC 7 Z9 7 U1 1 U2 2 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 EI 1996-8507 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2014 VL 24 IS 1 BP 313 EP 333 DI 10.5705/ss.2011.197 PG 21 WC Statistics & Probability SC Mathematics GA CC2MC UT WOS:000350178100016 PM 24478570 ER PT S AU Fritsche, LG Fariss, RN Stambolian, D Abecasis, GR Curcio, CA Swaroop, A AF Fritsche, Lars G. Fariss, Robert N. Stambolian, Dwight Abecasis, Goncalo R. Curcio, Christine A. Swaroop, Anand BE Chakravarti, A Green, E TI Age-Related Macular Degeneration: Genetics and Biology Coming Together SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 15 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE complex disease; genetic susceptibility; neurodegeneration; retina; blindness ID COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; GENOME-WIDE ASSOCIATION; SUBRETINAL DRUSENOID DEPOSITS; BRUCHS MEMBRANE; HIGH-RISK; RACIAL/ETHNIC GROUPS; NLRP3 INFLAMMASOME; CODING VARIANT; UNITED-STATES AB Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40-60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. C1 [Fritsche, Lars G.; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA. RP Swaroop, A (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. EM larsf@umich.edu; farissr@nei.nih.gov; stamboli@mail.med.upenn.edu; goncalo@umich.edu; curcio@uab.edu; swaroopa@nei.nih.gov OI Swaroop, Anand/0000-0002-1975-1141 FU Intramural NIH HHS; NEI NIH HHS [EY022005, EY023164, EY06109, R01 EY006109, R01 EY022005, R01 EY023164] NR 120 TC 78 Z9 78 U1 5 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3715-5 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2014 VL 15 BP 151 EP 171 DI 10.1146/annurev-genom-090413-025610 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA BB9LQ UT WOS:000348449500007 PM 24773320 ER PT S AU Platt, FM Wassif, C Colaco, A Dardis, A Lloyd-Evans, E Bembi, B Porter, FD AF Platt, Frances M. Wassif, Christopher Colaco, Alexandria Dardis, Andrea Lloyd-Evans, Emyr Bembi, Bruno Porter, Forbes D. BE Chakravarti, A Green, E TI Disorders of Cholesterol Metabolism and Their Unanticipated Convergent Mechanisms of Disease SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 15 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE cholesterol; sphingolipids; Smith-Lemli-Opitz syndrome; Niemann-Pick disease type C; Tangier disease ID LEMLI-OPITZ-SYNDROME; LOW-DENSITY-LIPOPROTEIN; SUBSTRATE REDUCTION THERAPY; 3-BETA-HYDROXYSTEROL DELTA(14)-REDUCTASE DEFICIENCY; MULTIPLE CONGENITAL-ANOMALIES; ABCA1-DEPENDENT LIPID EFFLUX; CENTRAL-NERVOUS-SYSTEM; CASSETTE TRANSPORTER 1; OF-THE-LITERATURE; PICK-C DISEASE AB Cholesterol plays a key role in many cellular processes, and is generated by cells through de novo biosynthesis or acquired from exogenous sources through the uptake of low-density lipoproteins. Cholesterol biosynthesis is a complex, multienzyme-catalyzed pathway involving a series of sequentially acting enzymes. Inherited defects in genes encoding cholesterol biosynthetic enzymes or other regulators of cholesterol homeostasis result in severe metabolic diseases, many of which are rare in the general population and currently without effective therapy. Historically, these diseases have been viewed as discrete disorders, each with its own genetic cause and distinct pathogenic cascades that lead to its specific clinical features. However, studies have recently shown that three of these diseases have an unanticipated mechanistic convergence. This surprising finding is not only shedding light on details of cellular cholesterol homeostasis but also suggesting novel approaches to therapy. C1 [Platt, Frances M.; Wassif, Christopher; Colaco, Alexandria] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. [Wassif, Christopher; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Dardis, Andrea; Bembi, Bruno] Univ Hosp Santa Maria della Misericordia, I-33100 Udine, Italy. [Lloyd-Evans, Emyr] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales. RP Platt, FM (reprint author), Univ Oxford, Dept Pharmacol, S Parks Rd, Oxford OX1 3QT, England. EM frances.platt@pharm.ox.ac.uk; fdporter@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 FU Intramural NIH HHS NR 141 TC 14 Z9 14 U1 0 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3715-5 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2014 VL 15 BP 173 EP 194 DI 10.1146/annurev-genom-091212-153412 PG 22 WC Genetics & Heredity SC Genetics & Heredity GA BB9LQ UT WOS:000348449500008 PM 25184529 ER PT S AU McEwen, JE Boyer, JT Sun, KY Rothenberg, KH Lockhart, NC Guyer, MS AF McEwen, Jean E. Boyer, Joy T. Sun, Kathie Y. Rothenberg, Karen H. Lockhart, Nicole C. Guyer, Mark S. BE Chakravarti, A Green, E TI The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: Reflections on an Ongoing Experiment SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 15 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE ELSI; bioethics; society; policy ID PREIMPLANTATION GENETIC DIAGNOSIS; CANCER-SOCIETY GUIDELINES; FOLLOW-UP CARE; INCIDENTAL FINDINGS; INFORMED-CONSENT; INHERITED PREDISPOSITION; ENHANCEMENT RESEARCH; HEALTH-INSURANCE; RECOMMENDATIONS; INFORMATION AB For more than 20 years, the Ethical, Legal, and Social Implications (ELSI) Program of the National Human Genome Research Institute has supported empirical and conceptual research to anticipate and address the ethical, legal, and social implications of genomics. As a component of the agency that funds much of the underlying science, the program has always been an experiment. The ever-expanding number of issues the program addresses and the relatively low level of commitment on the part of other funding agencies to support such research make setting priorities especially challenging. Program-supported studies have had a significant impact on the conduct of genomics research, the implementation of genomic medicine, and broader public policies. The program's influence is likely to grow as ELSI research, genomics research, and policy development activities become increasingly integrated. Achieving the benefits of increased integration while preserving the autonomy, objectivity, and intellectual independence of ELSI investigators presents ongoing challenges and new opportunities. C1 [McEwen, Jean E.; Boyer, Joy T.; Sun, Kathie Y.; Rothenberg, Karen H.; Lockhart, Nicole C.; Guyer, Mark S.] NHGRI, Bethesda, MD 20892 USA. [Rothenberg, Karen H.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA. RP McEwen, JE (reprint author), NHGRI, Bethesda, MD 20892 USA. EM mcewenj@mail.nih.gov; boyerj@mail.nih.gov; sunky@mail.nih.gov; rothenbergk@mail.nih.gov; lockhani@mail.nih.gov; guyerm@mail.nih.gov NR 147 TC 7 Z9 7 U1 3 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3715-5 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2014 VL 15 BP 481 EP + DI 10.1146/annurev-genom-090413-025327 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA BB9LQ UT WOS:000348449500021 PM 24773317 ER PT J AU Yokoyama, W Kohsaka, H Kaneko, K Walters, M Takayasu, A Fukuda, S Miyabe, C Miyabe, Y Love, PE Nakamoto, N Kanai, T Watanabe-Imai, K Charvat, TT Penfold, MET Jaen, J Schall, TJ Harigai, M Miyasaka, N Nanki, T AF Yokoyama, Waka Kohsaka, Hitoshi Kaneko, Kayoko Walters, Matthew Takayasu, Aiko Fukuda, Shin Miyabe, Chie Miyabe, Yoshishige Love, Paul E. Nakamoto, Nobuhiro Kanai, Takanori Watanabe-Imai, Kaori Charvat, Trevor T. Penfold, Mark E. T. Jaen, Juan Schall, Thomas J. Harigai, Masayoshi Miyasaka, Nobuyuki Nanki, Toshihiro TI Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID FIBROBLAST-LIKE SYNOVIOCYTES; CONTROLLED CLINICAL-TRIAL; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; SYNOVIAL FIBROBLASTS; CELL DEVELOPMENT; MACROPHAGES; ANTIBODY; TECK; DIFFERENTIATION AB Introduction: Biological drugs are effective in patients with rheumatoid arthritis (RA), but increase severe infections. The CC chemokine receptor (CCR) 9 antagonist was effective for Crohn's disease without critical adverse effects including infections in clinical trials. The present study was carried out to explore the pathogenic roles of chemokine (C-C motif) ligand (CCL) 25 and its receptor, CCR9, in autoimmune arthritis and to study if the CCR9 antagonist could be a new treatment for RA. Methods: CCL25 and CCR9 expression was examined with immunohistochemistry and Western blotting. Concentration of interleukin (IL)-6, matrix metalloproteinase (MMP)-3 and tumor necrosis factor (TNF)-alpha was measured with enzyme-linked immunosorbent assays. Effects of abrogating CCR9 on collagen-induced arthritis (CIA) was evaluated using CCR9-deficient mice or the CCR9 antagonist, CCX8037. Fluorescence labeled-CD11b(+) splenocytes from CIA mice were transferred to recipient CIA mice and those infiltrating into the synovial tissues of the recipient mice were counted. Results: CCL25 and CCR9 proteins were found in the RA synovial tissues. CCR9 was expressed on macrophages, fibroblast-like synoviocytes (FLS) and dendritic cells in the synovial tissues. Stimulation with CCL25 increased IL-6 and MMP-3 production from RA FLS, and IL-6 and TNF-alpha production from peripheral blood monocytes. CIA was suppressed in CCR9-deficient mice. CCX8037 also inhibited CIA and the migration of transferred CD11b(+) splenocytes into the synovial tissues. Conclusions: The interaction between CCL25 and CCR9 may play important roles in cell infiltration into the RA synovial tissues and inflammatory mediator production. Blocking CCL25 or CCR9 may represent a novel safe therapy for RA. C1 [Yokoyama, Waka; Kohsaka, Hitoshi; Kaneko, Kayoko; Takayasu, Aiko; Fukuda, Shin; Miyabe, Chie; Miyabe, Yoshishige; Watanabe-Imai, Kaori; Harigai, Masayoshi; Miyasaka, Nobuyuki] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Rheumatol, Bunkyo Ku, Tokyo 1108519, Japan. [Walters, Matthew; Charvat, Trevor T.; Penfold, Mark E. T.; Jaen, Juan; Schall, Thomas J.] ChemoCentryx Inc, Mountain View, CA 94043 USA. [Miyabe, Chie] Tokyo Med Univ, Dept Dermatol, Shinjuku Ku, Tokyo 1608402, Japan. [Love, Paul E.] NICHHD, NIH, Bethesda, MD 20892 USA. [Nakamoto, Nobuhiro; Kanai, Takanori] Keio Univ, Div Gastroenterol & Hepatol, Dept Internal Med,Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Nanki, Toshihiro] Teikyo Univ, Dept Clin Res Med, Itabashi Ku, Tokyo 1738605, Japan. RP Nanki, T (reprint author), Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Rheumatol, Bunkyo Ku, 1-5-45 Yusima, Tokyo 1108519, Japan. EM nanki@med.teikyo-u.ac.jp NR 43 TC 11 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 5 AR 445 DI 10.1186/s13075-014-0445-9 PG 9 WC Rheumatology SC Rheumatology GA CB8NC UT WOS:000349885900024 PM 25248373 ER PT J AU Houghton, LC Cooper, GD Bentley, GR Booth, M Chowdhury, OA Troisi, R Ziegler, RG Hoover, RN Katki, HA AF Houghton, Lauren C. Cooper, Gillian D. Bentley, Gillian R. Booth, Mark Chowdhury, Osul A. Troisi, Rebecca Ziegler, Regina G. Hoover, Robert N. Katki, Hormuzd A. TI A migrant study of pubertal timing and tempo in British-Bangladeshi girls at varying risk for breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID SECULAR TRENDS; PENALIZED LIKELIHOOD; BODY-MASS; ADRENARCHE; MATURATION; CHILDREN; MENARCHE; AGE; ASSOCIATION; ANDROGENS AB Introduction: Earlier menarche is related to subsequent breast cancer risk, yet international differences in the age and tempo of other pubertal milestones and their relationships with body mass index (BMI) are not firmly established in populations at differing risk for breast cancer. We compared age and tempo of adrenarche, thelarche, pubarche, and menarche in a migrant study of Bangladeshi girls to the United Kingdom (UK) and assessed whether differences by migration were explained by differences in BMI. Methods: Included were groups of Bangladeshi (n = 168), British-Bangladeshi (n = 174) and white British (n = 54) girls, aged 5 to 16 years. Interviewer-administered questionnaires obtained pubertal staging; height and weight were measured. Salivary dehydroepiandrosterone-sulfate concentrations >400 pg/ml defined adrenarche. Median ages of pubertal milestones and hazard ratios (HR) with 95% confidence intervals (CI) were estimated from Weibull survival models. Results: In all three groups, adrenarche occurred earliest, followed by thelarche, pubarche, and finally menarche. Neither median age at adrenarche (Bangladeshi = 7.2, British-Bangladeshi = 7.4, white British = 7.1; P-trend = 0.70) nor at menarche (Bangladeshi = 12.5, British-Bangladeshi = 12.1, white British = 12.6; P-trend = 0.70) differed across groups. In contrast, median age at thelarche (Bangladeshi = 10.7, British-Bangladeshi = 9.6, white British = 8.7; P-trend < 0.01) occurred earlier among girls living in the UK. Compared with Bangladeshi girls, HRs (95% CI) for earlier thelarche were 1.6 (1.1 to 2.4) for British-Bangladeshi girls and 2.6 (1.5 to 4.4) for white British girls (P-trend < 0.01), but were attenuated after adjustment for BMI (British-Bangladeshi = 1.1 (0.7 to 1.8), white British = 1.7(1.0 to 3.1); P-trend = 0.20). Conclusions: Thelarche occurred earlier, but puberty progressed slower with increasing exposure to the UK environment; differences were partially explained by greater BMI. The growth environment might account for much of the ethnic differences in pubertal development observed across and within countries. C1 [Houghton, Lauren C.; Troisi, Rebecca; Ziegler, Regina G.; Hoover, Robert N.; Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cooper, Gillian D.; Bentley, Gillian R.] Univ Durham, Dept Anthropol, Durham, England. [Cooper, Gillian D.; Bentley, Gillian R.] Univ Durham, Wolfson Res Inst Hlth & Wellbeing, Durham, England. [Booth, Mark] Univ Durham, Sch Med Pharm & Hlth, Durham, England. [Chowdhury, Osul A.] Sylhet MAG Osmani Med Coll, Sylhet, Bangladesh. RP Houghton, LC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM houghtonlc@mail.nih.gov FU NIH-Wellcome Trust Studentship; Intramural Office of Research at the National Cancer Institute/National Institutes of Health FX This research was funded by an NIH-Wellcome Trust Studentship (to LCH) and through the Intramural Office of Research at the National Cancer Institute/National Institutes of Health. The authors would like to acknowledge Shanaz Begum, Rita Platts and Lutfunnessa Tania for their assistance in fieldwork and the ABBY participants, their parents and the schools for their generous participation in the study. NR 43 TC 2 Z9 2 U1 3 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 6 AR 469 DI 10.1186/s13058-014-0469-8 PG 10 WC Oncology SC Oncology GA CB8NB UT WOS:000349885800008 PM 25398700 ER PT S AU Rybak, IA Molkov, YI Jasinski, PE Shevtsova, NA Smith, JC AF Rybak, Ilya A. Molkov, Yaroslav I. Jasinski, Patrick E. Shevtsova, Natalia A. Smith, Jeffrey C. BE Holstege, G Beers, CM Subramanian, HH TI Rhythmic Bursting in the Pre-Botzinger Complex: Mechanisms and Models SO CENTRAL NERVOUS SYSTEM CONTROL OF RESPIRATION SE Progress in Brain Research LA English DT Review; Book Chapter DE neural oscillations; respiration; persistent sodium current; calcium-activated nonspecific cation current; sodium-potassium pump ID METABOTROPIC GLUTAMATE RECEPTORS; MAMMALIAN RESPIRATORY NETWORK; DEPENDENT POTASSIUM CHANNELS; NONSPECIFIC CATION CURRENT; NEURONS IN-VITRO; PREBOTZINGER COMPLEX; PACEMAKER NEURONS; NEONATAL MICE; GENERATION; SODIUM AB The pre-Botzinger complex (pre-BotC), a neural structure involved in respiratory rhythm generation, can generate rhythmic bursting activity in vitro that persists after blockade of synaptic inhibition. Experimental studies have identified two mechanisms potentially involved in this activity: one based on the persistent sodium current (I-NaP) and the other involving calcium (I-Ca) and/or calcium-activated nonspecific cation (I-CAN) currents. In this modeling study, we investigated bursting generated in single neurons and excitatory neural populations with randomly distributed conductances of I-NaP and I-Ca. We analyzed the possible roles of these currents, the Na+/K+ pump, synaptic mechanisms, and network interactions in rhythmic bursting generated under different conditions. We show that a population of synaptically coupled excitatory neurons with randomly distributed I-NaP-and/or I-CAN-mediated burst generating mechanisms can operate in different oscillatory regimes with bursting dependent on either current or independent of both. The existence of multiple oscillatory regimes and their state dependence may explain rhythmic activities observed in the pre-BotC under different conditions. C1 [Rybak, Ilya A.; Molkov, Yaroslav I.; Jasinski, Patrick E.; Shevtsova, Natalia A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Molkov, Yaroslav I.] Indiana Univ Purdue Univ, Dept Math Sci, Indianapolis, IN 46202 USA. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Rybak, IA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. EM rybak@drexel.edu NR 40 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-63274-6 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2014 VL 209 BP 1 EP 23 DI 10.1016/B978-0-444-63274-6.00001-1 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BC0PU UT WOS:000349323900002 PM 24746040 ER PT S AU Shevtsova, NA Busselberg, D Molkov, YI Bischoff, AM Smith, JC Richter, DW Rybak, IA AF Shevtsova, Natalia A. Buesselberg, Dietrich Molkov, Yaroslav I. Bischoff, Anne M. Smith, Jeffrey C. Richter, Diethelm W. Rybak, Ilya A. BE Holstege, G Beers, CM Subramanian, HH TI Effects of Glycinergic Inhibition Failure on Respiratory Rhythm and Pattern Generation SO CENTRAL NERVOUS SYSTEM CONTROL OF RESPIRATION SE Progress in Brain Research LA English DT Review; Book Chapter DE computational modeling; respiratory rhythm; pre-Botzinger complex; glycinergic inhibition; apneusis; apnea; hypoxia; translational medicine ID PRE-BOTZINGER COMPLEX; OSCILLATOR MICE; NETWORK; MECHANISMS; INTERNEURONS; RECEPTORS; NEURONS; NEUROTRANSMITTERS; REORGANIZATION; HYPEREKPLEXIA AB Inhibitory interactions between neurons of the respiratory network are involved in rhythm generation and pattern formation. Using a computational model of brainstem respiratory networks, we investigated the possible effects of suppressing glycinergic inhibition on the activity of different respiratory neuron types. Our study revealed that progressive suppression of glycinergic inhibition affected all neurons of the network and disturbed neural circuits involved in termination of inspiration. Causal was a dysfunction of postinspiratory inhibition targeting inspiratory neurons, which often led to irregular preterm reactivation of these neurons, producing double or multiple short-duration inspiratory bursts. An increasing blockade of glycinergic inhibition led to apneustic inspiratory activity. Similar disturbances of glycinergic inhibition also occur during hypoxia. A clear difference in prolonged hypoxia, however, is that the rhythm terminates in expiratory apnea. The critical function of glycinergic inhibition for normal respiratory rhythm generation and the consequences of its reduction, including in pathological conditions, are discussed. C1 [Shevtsova, Natalia A.; Molkov, Yaroslav I.; Rybak, Ilya A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Buesselberg, Dietrich] Weill Cornell Med Coll Qatar, Doha, Qatar. [Molkov, Yaroslav I.] Indiana Univ Purdue Univ, Dept Math Sci, Indianapolis, IN 46202 USA. [Bischoff, Anne M.; Richter, Diethelm W.] Univ Gottingen, Dept Neuro & Sensory Physiol, D-37073 Gottingen, Germany. [Bischoff, Anne M.; Richter, Diethelm W.] Excellence Cluster Nanoscale Microscopy & Mol Phy, Gottingen, Germany. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Shevtsova, NA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. EM natalia.shevtsova@drexelmed.edu OI Molkov, Yaroslav/0000-0002-0862-1974; Busselberg, Dietrich/0000-0001-5196-3366 FU Intramural NIH HHS; NHLBI NIH HHS [R33 HL087377]; NINDS NIH HHS [R01 NS057815, R01 NS069220] NR 31 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-63274-6 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2014 VL 209 BP 25 EP 38 DI 10.1016/B978-0-444-63274-6.00002-3 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BC0PU UT WOS:000349323900003 PM 24746041 ER PT S AU Biancotto, A McCoy, JP AF Biancotto, Angelique McCoy, J. Philip BE Fienberg, HG Nolan, GP TI Studying the Human Immunome: The Complexity of Comprehensive Leukocyte Immunophenotyping SO HIGH-DIMENSIONAL SINGLE CELL ANALYSIS: MASS CYTOMETRY, MULTI-PARAMETRIC FLOW CYTOMETRY AND BIOINFORMATIC TECHNIQUES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID CHRONIC LYMPHOCYTIC-LEUKEMIA; REGULATORY T-CELLS; POLYCHROMATIC FLOW-CYTOMETRY; CELLULAR HIERARCHY; INFLAMMATION; NANOCRYSTALS; SUBSETS; BARRIER; SYSTEM; ASSAY AB A comprehensive study of the cellular components of the immune system requires both deep and broad immunophenotyping of numerous cell populations in an efficient and practical manner. In this chapter, we describe the technical aspects of studying the human immunome using high-dimensional (15 color) fluorescence-based immunophenotyping. We focus on the technical aspects of polychromatic flow cytometry and the initial stages in developing a panel for comprehensive leukocyte immunophenotyping (CLIP). We also briefly discuss how this panel is being used and the challenges of encyclopedic analysis of these rich data sets. C1 [Biancotto, Angelique; McCoy, J. Philip] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. RP McCoy, JP (reprint author), NIH, Ctr Human Immunol Autoimmun & Inflammat, 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA. EM mccoyj@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999, ZIC HL005905-07] NR 40 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-54827-7; 978-3-642-54826-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2014 VL 377 BP 23 EP 60 DI 10.1007/82_2013_336 D2 10.1007/978-3-642-54827-7 PG 38 WC Oncology; Immunology SC Oncology; Immunology GA BC0DT UT WOS:000348978100003 PM 23975032 ER PT J AU Tuna, MM Dogan, BA Karakilic, E Arduc, A Isik, S Yilmaz, FM Topcuoglu, C Berker, D Guler, S AF Tuna, Mazhar Muslum Dogan, Berem Ayiek Karakilic, Ersen Arduc, Ayse Isik, Serhat Yilmaz, Fatma Meric Topcuoglu, Canan Berker, Dilek Guler, Serdar TI Evaluation of adipocytokine levels and vascular functions in young aged to middle aged men with idiopathic hypogonadotrophic hypogonadism SO NEUROENDOCRINOLOGY LETTERS LA English DT Article DE adipocytokine; vascular functions; hypogonadotrophic hypogonadism ID TESTOSTERONE REPLACEMENT THERAPY; FLOW-MEDIATED VASODILATION; ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; ADIPONECTIN LEVELS; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; BRACHIAL-ARTERY; LEPTIN; REACTIVITY AB OBJECTIVE: Hypogonadism has major effects on the urogenital system, in addition to other systems, the cardiovascular system in particular. There have been few studies conducted on markers of atherosclerosis, such as flow mediated dilatation (% FMD), carotid intima-media thickness (CIMT) and adipocytokine levels in idiopatic hypogonadotropic hypogonadal (IHH) males mostly in adult patients. The aim of this study was to evaluate the relationship between androgens and adipocytokines and parameters of vascular functions in hypogonadal men. MATERIALS AND METHODS: The study population consisted of 11 treatment naive IHH patients (group 1) and 15 age-matched healthy control males (group 2). A fasting blood sample was obtained for leptin, adiponectin and resistin. The endothelial functions were evaluated by studying % FMD and CIMT by high resolution B-mode ultrasound. RESULTS: No significant differences in age, body mass index, systolic and diastolic blood pressure were recorded between the two groups. The leptin level was significantly higher in group 1, whereas adiponectin and resistin levels were same between two groups. There was a negative correlation between total testosterone and carotid intima-media thickness (r=-0.656, p=0.008), and a negative correlation between total testosterone and leptin level (r=-0.794, p<0.001). No correlation was found between leptin and CIMT (p=0.184). CONCLUSION: Testosterone deficiency in hypogonadal men is associated with vascular parameters of atherosclerosis. The findings may establish indications for testosterone replacement therapy in hypogonadal men. C1 [Tuna, Mazhar Muslum] Dicle Univ, Fac Med, Dept Endocrinol & Metab, Diyarbakir, Turkey. [Dogan, Berem Ayiek; Karakilic, Ersen; Isik, Serhat; Berker, Dilek] Ankara Numune Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey. [Arduc, Ayse] Natl Inst Diabet & Digest & Kidney Dis, NIH, Endocrine & Obes Branch, Washington, DC USA. [Yilmaz, Fatma Meric; Topcuoglu, Canan] Ankara Numune Training & Res Hosp, Dept Med Biochem, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Fac Med, Dept Endocrinol & Metab, Corum, Turkey. RP Tuna, MM (reprint author), Dicle Univ, Fac Med, Div Endocrinol & Metab, Diyarbakir, Turkey. EM tunamazhar@gmail.com FU Ankara Numune Training and Research Hospital FX This work was partially supported by grants from Ankara Numune Training and Research Hospital. NR 29 TC 2 Z9 2 U1 0 U2 1 PU MAGHIRA & MAAS PUBLICATIONS PI STOCKHOLM PA PO BOX 26132, S-100 41 STOCKHOLM, SWEDEN SN 0172-780X J9 NEUROENDOCRINOL LETT JI Neuroendocrinol. Lett. PY 2014 VL 35 IS 7 BP 640 EP 644 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CB1JY UT WOS:000349384700013 PM 25617889 ER PT S AU Christie, D Zhu, JF AF Christie, Darah Zhu, Jinfang BE Ellmeier, W Taniuchi, I TI Transcriptional Regulatory Networks for CD4 T Cell Differentiation SO TRANSCRIPTIONAL CONTROL OF LINEAGE DIFFERENTIATION IN IMMUNE CELLS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID ROR-GAMMA-T; NF-KAPPA-B; FOLLICULAR-HELPER-CELLS; ARYL-HYDROCARBON RECEPTOR; PATHOGENIC T(H)17 CELLS; TH2 CYTOKINE PRODUCTION; HYPER-IGE SYNDROME; IN-VIVO; INTERFERON-GAMMA; GENE-EXPRESSION AB CD4(+) T cells play a central role in controlling the adaptive immune response by secreting cytokines to activate target cells. Naive CD4(+) T cells differentiate into at least four subsets, Th1, Th2, Th17, and inducible regulatory T cells, each with unique functions for pathogen elimination. The differentiation of these subsets is induced in response to cytokine stimulation, which is translated into Stat activation, followed by induction of master regulator transcription factors. In addition to these factors, multiple other transcription factors, both subset specific and shared, are also involved in promoting subset differentiation. This review will focus on the network of transcription factors that control CD4(+) T cell differentiation. C1 [Christie, Darah; Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Christie, D (reprint author), NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM darah.christie@nih.gov; jfzhu@niaid.nih.gov RI Taniuchi, Ichiro/N-6399-2015; Zhu, Jinfang/B-7574-2012 OI Taniuchi, Ichiro/0000-0002-9853-9068; FU Intramural NIH HHS [ZIA AI001169-03] NR 252 TC 9 Z9 9 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-319-07395-8; 978-3-319-07394-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2014 VL 381 BP 125 EP 172 DI 10.1007/82_2014_372 D2 10.1007/978-3-319-07395-8 PG 48 WC Immunology SC Immunology GA BC0DW UT WOS:000348979600006 PM 24839135 ER PT S AU Bonelli, M Shih, HY Hirahara, K Singelton, K Laurence, A Poholek, A Hand, T Mikami, Y Vahedi, G Kanno, Y O'Shea, JJ AF Bonelli, Michael Shih, Han-Yu Hirahara, Kiyoshi Singelton, Kentner Laurence, Arian Poholek, Amanda Hand, Tim Mikami, Yohei Vahedi, Golnaz Kanno, Yuka O'Shea, John J. BE Ellmeier, W Taniuchi, I TI Helper T Cell Plasticity: Impact of Extrinsic and Intrinsic Signals on Transcriptomes and Epigenomes SO TRANSCRIPTIONAL CONTROL OF LINEAGE DIFFERENTIATION IN IMMUNE CELLS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID GROWTH-FACTOR-BETA; HISTONE DEACETYLASE INHIBITOR; PATHOGENIC T(H)17 CELLS; LONG NONCODING RNAS; EMBRYONIC STEM-CELLS; INTERFERON-REGULATORY FACTOR-4; SEGMENTED FILAMENTOUS BACTERIA; ARYL-HYDROCARBON RECEPTOR; TGF-BETA; IN-VIVO AB CD4(+) helper T cells are crucial for autoimmune and infectious diseases; however, the recognition of the many, diverse fates available continues unabated. Precisely what controls specification of helper T cells and preserves phenotypic commitment is currently intensively investigated. In this review, we will discuss the major factors that impact helper T cell fate choice, ranging from cytokines and the microbiome to metabolic control and epigenetic regulation. We will also discuss the technological advances along with the attendant challenges presented by "big data," which allow the understanding of these processes on comprehensive scales. C1 [Bonelli, Michael; Shih, Han-Yu; Singelton, Kentner; Laurence, Arian; Poholek, Amanda; Mikami, Yohei; Vahedi, Golnaz; Kanno, Yuka; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Hirahara, Kiyoshi] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chuo Ku, Chiba 2608670, Japan. [Hand, Tim] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Laurence, Arian/A-8770-2009; Taniuchi, Ichiro/N-6399-2015; Hirahara, Kiyoshi/E-2460-2017; OI Laurence, Arian/0000-0003-0942-8292; Taniuchi, Ichiro/0000-0002-9853-9068; Hirahara, Kiyoshi/0000-0002-9128-9449; Kanno, Yuka/0000-0001-5668-9319 FU Intramural NIH HHS [ZIA AR041159-06] NR 342 TC 7 Z9 7 U1 2 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-319-07395-8; 978-3-319-07394-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2014 VL 381 BP 279 EP 326 DI 10.1007/82_2014_371 D2 10.1007/978-3-319-07395-8 PG 48 WC Immunology SC Immunology GA BC0DW UT WOS:000348979600011 PM 24831346 ER PT S AU Croteau, DL Popuri, V Opresko, PL Bohr, VA AF Croteau, Deborah L. Popuri, Venkateswarlu Opresko, Patricia L. Bohr, Vilhelm A. BE Kornberg, RD TI Human RecQ Helicases in DNA Repair, Recombination, and Replication SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 83 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE RECQL1; BLM; WRN; RECQL4; RECQL5; genome stability ID WERNER-SYNDROME PROTEIN; ROTHMUND-THOMSON-SYNDROME; DOUBLE-STRAND BREAKS; BLOOMS-SYNDROME HELICASE; BASE EXCISION-REPAIR; WRN EXONUCLEASE ACTIVITY; TOPOISOMERASE-II-ALPHA; SYNDROME GENE-PRODUCT; END-JOINING PATHWAYS; COMMON FRAGILE SITES AB RecQ helicases are an important family of genome surveillance proteins conserved from bacteria to humans. Each of the five human RecQ helicases plays critical roles in genome maintenance and stability, and the RecQ protein family members are often referred to as guardians of the genome. The importance of these proteins in cellular homeostasis is underscored by the fact that defects in BLM, WRN, and RECQL4 are linked to distinct heritable human disease syndromes. Each human RecQ helicase has a unique set of protein-interacting partners, and these interactions dictate its specialized functions in genome maintenance, including DNA repair, recombination, replication, and transcription. Human RecQ helicases also interact with each other, and these interactions have significant impact on enzyme function. Future research goals in this field include a better understanding of the division of labor among the human RecQ helicases and learning how human RecQ helicases collaborate and cooperate to enhance genome stability. C1 [Croteau, Deborah L.; Popuri, Venkateswarlu; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Opresko, Patricia L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. RP Croteau, DL (reprint author), NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Opresko, Patricia/0000-0002-6470-2189 FU Intramural NIH HHS [ZIA AG000721-05, ZIA AG000726-21] NR 304 TC 103 Z9 104 U1 10 U2 31 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0883-4 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2014 VL 83 BP 519 EP 552 DI 10.1146/annurev-biochem-060713-035428 PG 34 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB9LE UT WOS:000348432500021 PM 24606147 ER PT S AU Storz, G Wolf, YI Ramamurthi, KS AF Storz, Gisela Wolf, Yuri I. Ramamurthi, Kumaran S. BE Kornberg, RD TI Small Proteins Can No Longer Be Ignored SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 83 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE membrane; cell division; sporulation; transport; signal transduction; protein ID OPEN READING FRAMES; CELL-DIVISION MACHINERY; CYTOCHROME BD OXIDASE; KINASE INHIBITOR SDA; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; SMALL RNA; MEMBRANE-PROTEIN; CAULOBACTER-CRESCENTUS; BACTERIAL CYTOKINESIS AB Small proteins, here defined as proteins of 50 amino acids or fewer in the absence of processing, have traditionally been overlooked due to challenges in their annotation and biochemical detection. In the past several years, however, increasing numbers of small proteins have been identified either through the realization that mutations in intergenic regions are actually within unannotated small protein genes or through the discovery that some small, regulatory RNAs encode small proteins. These insights, together with comparative sequence analysis, indicate that tens if not hundreds of small proteins are synthesized in a given organism. This review summarizes what has been learned about the functions of several of these bacterial small proteins, most of which act at the membrane, illustrating the astonishing range of processes in which these small proteins act and suggesting several general conclusions. Important questions for future studies of these overlooked proteins are also discussed. C1 [Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. [Wolf, Yuri I.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM storzg@mail.nih.gov; ramamurthiks@mail.nih.gov RI Ramamurthi, Kumaran/P-3516-2015; OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS [Z99 LM999999, ZIA BC011211-05, ZIA HD008855-06, ZIA HD008855-07, ZIA HD008855-08] NR 108 TC 36 Z9 36 U1 2 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0883-4 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2014 VL 83 BP 753 EP + DI 10.1146/annurev-biochem-070611-102400 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB9LE UT WOS:000348432500029 PM 24606146 ER PT S AU Hinnebusch, AG AF Hinnebusch, Alan G. BE Kornberg, RD TI The Scanning Mechanism of Eukaryotic Translation Initiation SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 83 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE translation; initiation; scanning; ribosome; eIFs; tRNA ID 40S RIBOSOMAL-SUBUNIT; START CODON SELECTION; RNA RECOGNITION MOTIF; C-TERMINAL DOMAIN; FACTOR 3 EIF3; MAMMALIAN PROTEIN-SYNTHESIS; STRINGENT AUG SELECTION; GTP EXCHANGE FACTORS; GENOME-WIDE ANALYSIS; MESSENGER-RNA AB In eukaryotes, the translation initiation codon is generally identified by the scanning mechanism, wherein every triplet in the messenger RNA leader is inspected for complementarity to the anticodon of methionyl initiator transfer RNA (Met-tRNAi). Binding of Met-tRNAi to the small (40S) ribosomal subunit, in a ternary complex (TC) with eIF2-GTP, is stimulated by eukaryotic initiation factor 1 (eIF1), eIF1A, eIF3, and eIF5, and the resulting preinitiation complex (PIC) joins the 5' end of mRNA preactivated by eIF4F and poly(A)-binding protein. RNA helicases remove secondary structures that impede ribosome attachment and subsequent scanning. Hydrolysis of eIF2-bound GTP is stimulated by eIF5 in the scanning PIC, but completion of the reaction is impeded at non-AUG triplets. Although eIF1 and eIF1A promote scanning, eIF1 and possibly the C-terminal tail of eIF1A must be displaced from the P decoding site to permit base-pairing between Met-tRNAi and the AUG codon, as well as to allow subsequent phosphate release from eIF2-GDP. A second GTPase, eIF5B, catalyzes the joining of the 60S subunit to produce an 80S initiation complex that is competent for elongation. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 246 TC 133 Z9 134 U1 12 U2 46 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0883-4 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2014 VL 83 BP 779 EP 812 DI 10.1146/annurev-biochem-060713-035802 PG 34 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB9LE UT WOS:000348432500030 PM 24499181 ER PT S AU Shcherbakova, DM Sengupta, P Lippincott-Schwartz, J Verkhusha, VV AF Shcherbakova, Daria M. Sengupta, Prabuddha Lippincott-Schwartz, Jennifer Verkhusha, Vladislav V. BE Dill, KA TI Photocontrollable Fluorescent Proteins for Superresolution Imaging SO ANNUAL REVIEW OF BIOPHYSICS, VOL 43 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE PALM; RESOLFT; PAGFP; PAmCherry; EosFP ID PHOTOACTIVATED LOCALIZATION MICROSCOPY; SINGLE-MOLECULE LOCALIZATION; STRUCTURED-ILLUMINATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; GENETICALLY EXPRESSED PROBES; PAIR-CORRELATION-ANALYSIS; DIFFRACTION BARRIER; RATIONAL DESIGN; MARKER PROTEIN; CELL-MEMBRANES AB Superresolution fluorescence microscopy permits the study of biological processes at scales small enough to visualize fine subcellular structures that are unresolvable by traditional diffraction-limited light microscopy. Many superresolution techniques, including those applicable to live cell imaging, utilize genetically encoded photocontrollable fluorescent proteins. The fluorescence of these proteins can be controlled by light of specific wavelengths. In this review, we discuss the biochemical and photophysical properties of photocontrollable fluorescent proteins that are relevant to their use in superresolution microscopy. We then describe the recently developed photoactivatable, photoswitchable, and reversibly photoswitchable fluorescent proteins, and we detail their particular usefulness in single-molecule localization-based and nonlinear ensemble-based superresolution techniques. Finally, we discuss recent applications of photocontrollable proteins in superresolution imaging, as well as how these applications help to clarify properties of intracellular structures and processes that are relevant to cell and developmental biology, neuroscience, cancer biology and biomedicine. C1 [Shcherbakova, Daria M.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. [Shcherbakova, Daria M.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10461 USA. [Sengupta, Prabuddha; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Shcherbakova, DM (reprint author), Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. EM lippincj@mail.nih.gov; vladislav.verkhusha@einstein.yu.edu OI Sengupta, Prabuddha/0000-0001-7094-6967 FU Intramural NIH HHS [Z99 HD999999]; NCI NIH HHS [CA164468, R01 CA164468]; NIBIB NIH HHS [EB013571, R01 EB013571]; NIGMS NIH HHS [GM073913, R01 GM073913] NR 88 TC 41 Z9 42 U1 4 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1843-7 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2014 VL 43 BP 303 EP 329 DI 10.1146/annurev-biophys-051013-022836 PG 27 WC Biophysics SC Biophysics GA BB9LG UT WOS:000348434000014 PM 24895855 ER PT S AU Qi, H Kastenmuller, W Germain, RN AF Qi, Hai Kastenmueller, Wolfgang Germain, Ronald N. BE Schekman, R Lehmann, R TI Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE lymph node; imaging; innate lymphoid cells; chemokines; myeloid cells; lymphocytes ID CD8(+) T-CELLS; SUBCAPSULAR SINUS MACROPHAGES; FOLLICULAR DENDRITIC CELLS; CENTER B-CELL; CHEMOKINE RECEPTOR CXCR3; ANTIGEN-PRESENTING CELLS; NATURAL-KILLER-CELLS; GERMINAL-CENTER; IN-VIVO; HELPER-CELL AB Secondary lymphoid tissues are the sites of both innate and adaptive host defense. Aside from the relatively static nonhematopoietic stromal elements and some macrophages and dendritic cells, most of the cells in these tissues are in constant movement, but the organs maintain a defined microanatomy with preferred locations for the bulk of T cells, Bcells, and other lymphocytes and subsets of myeloid cells. Here we describe both the cell dynamics and spatial organization of lymph nodes and review how both physical features and molecular cues guide cell movement to optimize host defense. We emphasize the role of locality in improving the efficiency of a system requiring rare cells to find each other and interact productively through membrane-bound or short-range secreted mediators and highlight how changes in steady-state cell positioning during an infectious challenge contribute to rapid generation of productive responses. C1 [Qi, Hai] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Lab Dynam Immunobiol, Beijing 100084, Peoples R China. [Kastenmueller, Wolfgang] Univ Bonn, Inst Mol Med, D-53105 Bonn, Germany. [Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Qi, H (reprint author), Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Lab Dynam Immunobiol, Beijing 100084, Peoples R China. EM qihai@biomed.tsinghua.edu.cn; wkastenm@uni-bonn.de; rgermain@nih.gov FU Intramural NIH HHS NR 171 TC 22 Z9 23 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3130-6 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2014 VL 30 BP 141 EP 167 DI 10.1146/annurev-cellbio-100913-013254 PG 27 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BB9LH UT WOS:000348434900008 PM 25150013 ER PT S AU Schoenebeck, JJ Ostrander, EA AF Schoenebeck, Jeffrey J. Ostrander, Elaine A. BE Schekman, R Lehmann, R TI Insights into Morphology and Disease from the Dog Genome Project SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE morphology; skull; body size; breed standard; disease; genomics ID MITRAL-VALVE DISEASE; DOMESTIC DOG; WIDE ASSOCIATION; DILATED CARDIOMYOPATHY; LINKAGE DISEQUILIBRIUM; GROWTH-HORMONE; SUSCEPTIBILITY LOCI; DOBERMAN-PINSCHERS; NEGATIVE REGULATOR; SUBAORTIC STENOSIS AB Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous. C1 [Schoenebeck, Jeffrey J.; Ostrander, Elaine A.] NHGRI, Canc Genet & Comparat Genom Branch, Bethesda, MD 20892 USA. [Schoenebeck, Jeffrey J.] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland. [Schoenebeck, Jeffrey J.] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9RG, Midlothian, Scotland. RP Schoenebeck, JJ (reprint author), NHGRI, Canc Genet & Comparat Genom Branch, Bethesda, MD 20892 USA. EM jeffrey.schoenebeck@roslin.ed.ac.uk; eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 148 TC 16 Z9 16 U1 13 U2 60 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3130-6 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2014 VL 30 BP 535 EP 560 DI 10.1146/annurev-cellbio-100913-012927 PG 26 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BB9LH UT WOS:000348434900022 PM 25062362 ER PT S AU Weller, SK Sawitzke, JA AF Weller, Sandra K. Sawitzke, James A. BE Gottesman, S TI Recombination Promoted by DNA Viruses: Phage lambda to Herpes Simplex Virus SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 68 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE DNA replication; concatemer formation; single-strand annealing; exonucleases; single-strand annealing proteins; recombineering ID SINGLE-STRANDED-DNA; TYPE-1 ALKALINE NUCLEASE; TEMPERATURE-SENSITIVE MUTANTS; FIELD GEL-ELECTROPHORESIS; DEPENDENT PROTEIN-KINASE; COLI RECT PROTEIN; BACTERIOPHAGE-LAMBDA; ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; BINDING-PROTEIN AB The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage lambda and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on lambda and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. C1 [Weller, Sandra K.] Univ Connecticut, Ctr Hlth, Dept Mol Biol & Biophys, Farmington, CT 06030 USA. [Sawitzke, James A.] NCI, Mol Control & Genet Sect, NIH, Frederick, MD 21702 USA. RP Weller, SK (reprint author), Univ Connecticut, Ctr Hlth, Dept Mol Biol & Biophys, Farmington, CT 06030 USA. EM weller@uchc.edu; sawitzkj@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E]; NIAID NIH HHS [AI021747, AI069136, R01 AI021747, R01 AI069136, R37 AI021747]; PHS HHS [HHSN261200800001E] NR 160 TC 9 Z9 9 U1 1 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1168-1 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2014 VL 68 BP 237 EP 258 DI 10.1146/annurev-micro-091313-103424 PG 22 WC Microbiology SC Microbiology GA BB9LU UT WOS:000348452900014 PM 25002096 ER PT S AU Hikosaka, O Kim, HF Yasuda, M Yamamoto, S AF Hikosaka, Okihide Kim, Hyoung F. Yasuda, Masaharu Yamamoto, Shinya BE Hyman, SE TI Basal Ganglia Circuits for Reward Value-Guided Behavior SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 37 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE caudate nucleus; substantia nigra; superior colliculus; flexible value; stable value; visual object ID NIGRA PARS RETICULATA; SACCADIC EYE-MOVEMENTS; MONKEY CAUDATE-NUCLEUS; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; OCULOMOTOR FUNCTIONS; SUPERIOR COLLICULUS; AUDITORY RESPONSES; NEURAL MECHANISMS; STRIATAL NEURONS AB The basal ganglia are equipped with inhibitory and disinhibitory mechanisms that enable a subject to choose valuable objects and actions. Notably, a value can be determined flexibly by recent experience or stably by prolonged experience. Recent studies have revealed that the head and tail of the caudate nucleus selectively and differentially process flexible and stable values of visual objects. These signals are sent to the superior colliculus through different parts of the substantia nigra so that the animal looks preferentially at high-valued objects, but in different manners. Thus, relying on short-term value memories, the caudate head circuit allows the subject's gaze to move expectantly to recently valued objects. Relying on long-term value memories, the caudate tail circuit allows the subject's gaze to move automatically to previously valued objects. The basal ganglia also contain an equivalent parallel mechanism for action values. Such flexible-stable parallel mechanisms for object and action values create a highly adaptable system for decision making. C1 [Hikosaka, Okihide; Kim, Hyoung F.; Yasuda, Masaharu; Yamamoto, Shinya] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Yamamoto, Shinya] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058568, Japan. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov RI Yamamoto, Shinya/S-3134-2016 OI Yamamoto, Shinya/0000-0002-0505-8848 FU Intramural NIH HHS [ZIA EY000415-11] NR 107 TC 33 Z9 33 U1 7 U2 25 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2437-7 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2014 VL 37 BP 289 EP + DI 10.1146/annurev-neuro-071013-013924 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BB9LX UT WOS:000348454500016 PM 25032497 ER PT S AU Parrow, NL Fleming, RE AF Parrow, Nermi L. Fleming, Robert E. BE Cousins, RJ TI Bone Morphogenetic Proteins as Regulators of Iron Metabolism SO ANNUAL REVIEW OF NUTRITION, VOL 34 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE bone morphogenic proteins; iron homeostasis; hepcidin; hereditary hemochromatosis ID PROTEASE MATRIPTASE-2 TMPRSS6; HEPATIC HEPCIDIN EXPRESSION; TRANSFERRIN RECEPTOR 2; BETA-THALASSEMIA; HEREDITARY HEMOCHROMATOSIS; OSTEOBLAST DIFFERENTIATION; HYPOTRANSFERRINEMIC MICE; POSITIVE REGULATION; GENE-EXPRESSION; BMP ANTAGONIST AB Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily of signaling molecules. In addition to protean roles in embryonic development, germ-line specification, and cellular differentiation, a central role in iron homeostasis has recently been demonstrated for certain BMPs. Specifically, BMP6 serves to relate hepatic iron stores to the hepatocellular expression of the iron-regulatory hormone hepcidin. This regulation occurs via cellular SMAD-signaling molecules and is strongly modulated by the BMP coreceptor hemojuvelin (HJV). Mutations in certain genes influencing signaling to hepcidin via the BMP/SMAD pathway are associated with human disorders of iron metabolism, such as hereditary hemochromatosis and iron-refractory iron-deficiency anemia. Evidence suggests that signals in addition to iron stores influence hepcidin expression via the BMP/SMAD pathway. This review summarizes the details of BMP/SMAD signaling, with a particular focus on its role in iron homeostasis and iron-related diseases. C1 [Parrow, Nermi L.] NIDDK, Div Mol & Clin Nutr, NIH, Bethesda, MD 20892 USA. [Fleming, Robert E.] St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. [Fleming, Robert E.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Fleming, RE (reprint author), St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. EM flemingr@slu.edu FU Intramural NIH HHS NR 76 TC 20 Z9 20 U1 1 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2834-4 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2014 VL 34 BP 77 EP 94 DI 10.1146/annurev-nutr-071813-105646 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BB9MA UT WOS:000348455800004 PM 24995692 ER PT S AU Ross, SA Davis, CD AF Ross, Sharon A. Davis, Cindy D. BE Cousins, RJ TI The Emerging Role of microRNAs and Nutrition in Modulating Health and Disease SO ANNUAL REVIEW OF NUTRITION, VOL 34 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE microRNA; diet; nutrition; cancer; cardiovascular disease; diabetes; obesity ID PANCREATIC-CANCER CELLS; HIGH-FAT DIET; INFLAMMATORY GENE-EXPRESSION; UP-REGULATION; PROSTATE-CANCER; 1,25-DIHYDROXYVITAMIN D-3; CIRCULATING MICRORNAS; TUMOR-SUPPRESSOR; DOWN-REGULATION; COLON-CANCER AB Understanding the molecular mechanisms that inform how diet and dietary supplements influence health and disease is an active research area. One such mechanism concerns the role of diet in modulating the activity and function of microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that are involved in posttranscriptional gene silencing and have been shown to control gene expression in diverse biological processes including development, differentiation, cell proliferation, metabolism, and inflammation as well as in human diseases. Recent evidence described in this review highlights how dietary factors may influence cancer, cardiovascular disease, type 2 diabetes mellitus, obesity, and nonalcoholic fatty liver disease through modulation of miRNA expression. Additionally, circulating miRNAs are emerging as putative biomarkers of disease, susceptibility, and perhaps dietary exposure. Research needs to move beyond associations in cells and animals to understanding the direct effects of diet and dietary supplements on miRNA expression and function in human health and disease. C1 [Ross, Sharon A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Davis, Cindy D.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. EM rosssha@mail.nih.gov; davisci@od.nih.gov NR 162 TC 20 Z9 21 U1 0 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2834-4 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2014 VL 34 BP 305 EP 336 DI 10.1146/annurev-nutr-071813-105729 PG 32 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BB9MA UT WOS:000348455800013 PM 25033062 ER PT S AU Brannon, PM Taylor, CL Coates, PM AF Brannon, Patsy M. Taylor, Christine L. Coates, Paul M. BE Cousins, RJ TI Use and Applications of Systematic Reviews in Public Health Nutrition SO ANNUAL REVIEW OF NUTRITION, VOL 34 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE systematic review; evidence-based review; public health nutrition; nutrition policy; nutrition guidelines ID COMPLEX INTERVENTIONS; METAANALYSIS; METHODOLOGY; GUIDELINES; SUPPORT; FIELD; ASSOCIATION; CHALLENGES; PREVENTION; OUTCOMES AB Decisions related to a spectrum of nutrition-related public health and clinical concerns must consider many factors and are best informed by evaluating the totality and quality of the evidence. Systematic review (SR) is a structured process to evaluate, compare, and synthesize relevant evidence for the SR-specific question(s). Applications of SR are exemplified here through the discussion of four case studies: research agendas, nutrient reference intakes, dietary guidance, and practice guidelines. Concerns that SR cannot be effectively applied to nutrition evidence because of the lack of an unexposed comparator and the complex homeostasis in nutrition are discussed. Central to understanding the applicability of SR is its flexibility in defining key inclusion criteria and rigorous elements as appropriate for the SR-specific question(s). Through the reduction of bias and random error by explicit, reproducible, comprehensive, and rigorous examination of all of the evidence, SR informs the scientific judgment needed for sound evidence-based public health nutrition. C1 [Brannon, Patsy M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Taylor, Christine L.; Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. EM CoatesP@od.nih.gov NR 64 TC 1 Z9 1 U1 2 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2834-4 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2014 VL 34 BP 401 EP 419 DI 10.1146/annurev-nutr-080508-141240 PG 19 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BB9MA UT WOS:000348455800017 PM 24819324 ER PT J AU Gandhi, AS Zhu, MS Pang, SK Wohlfarth, A Scheidweiler, KB Huestis, MA AF Gandhi, Adarsh S. Zhu, Mingshe Pang, Shaokun Wohlfarth, Ariane Scheidweiler, Karl B. Huestis, Marilyn A. TI Metabolite profiling of RCS-4, a novel synthetic cannabinoid designer drug, using human hepatocyte metabolism and TOF-MS SO BIOANALYSIS LA English DT Article ID TANDEM MASS-SPECTROMETRY; ORAL FLUID; LC-MS/MS; URINARY METABOLITES; HUMAN HAIR; IDENTIFICATION; JWH-073; MIXTURES; QUANTIFICATION; AFFINITY AB Background: Since 2009, scheduling legislation of synthetic cannabinoids prompted new compound emergence to circumvent legal restrictions. 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4) is a potent cannabinoid receptor agonist sold in herbal smoking blends. Absence of parent synthetic cannabinoids in urine suggests the importance of metabolite identification for detecting RCS-4 consumption in clinical and forensic investigations. Materials & methods & Results: With 1 h human hepatocyte incubation and TOF high-resolution MS, we identified 18 RCS-4 metabolites, many not yet reported. Most metabolites were hydroxylated with or without demethylation, carboxylation and dealkylation followed by glucuronidation. One additional sulfated metabolite was also observed. O-demethylation was the most common biotransformation and generated the major metabolite. Conclusion: For the first time, we present a metabolic scheme of RCS-4 obtained from human hepatocytes, including PhaseI and II metabolites. Metabolite structural information and associated high-resolution mass spectra can be employed for developing clinical and forensic laboratory RCS-4 urine screening methods. C1 [Gandhi, Adarsh S.; Wohlfarth, Ariane; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Zhu, Mingshe] Bristol Myers Squibb Res & Dev, Dept Biotransformat, Princeton, NJ 08543 USA. [Pang, Shaokun] AB SCIEX, Redwood City, CA 94404 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 39 TC 11 Z9 11 U1 2 U2 12 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 11 BP 1471 EP 1485 DI 10.4155/bio.14.13 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8OG UT WOS:000349179900013 PM 25046048 ER PT J AU Concheiro-Guisan, A Concheiro, M AF Concheiro-Guisan, Ana Concheiro, Marta TI Bioanalysis during pregnancy: recent advances and novel sampling strategies SO BIOANALYSIS LA English DT Review ID TANDEM MASS-SPECTROMETRY; UMBILICAL-CORD TISSUE; UTERO DRUG EXPOSURE; ACID ETHYL-ESTERS; NEONATAL ABSTINENCE SYNDROME; PRENATAL COCAINE EXPOSURE; OF-THE-ART; LC-MS-MS; LIQUID-CHROMATOGRAPHY; HAIR-ANALYSIS AB Consumption of drugs of abuse, tobacco and alcohol throughout pregnancy is a serious public health problem and results in an important economic cost to the health system. Drug and/or metabolites determination in biological matrices from mother and newborn is an objective measure of in utero drug exposure. We reviewed methods published for the determination of in utero drug exposure from 2007 to 2014, with special focus on meconium, placenta, umbilical cord and newborn hair. Accurate bioanalytical procedures are essential to obtain high-quality data to perform interventions and to establish correlations between analytical measures and clinical outcomes. We included a brief overview of clinical implications of in utero drug exposure to better understand the importance of this serious health issue. C1 [Concheiro-Guisan, Ana] Complejo Hosp Univ Vigo, Secc Neonatol, Vigo, Spain. [Concheiro, Marta] NIDA, Dept Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA. RP Concheiro, M (reprint author), NIDA, Dept Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA. EM marta.concheiro@gmail.com NR 101 TC 3 Z9 3 U1 0 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 23 SI SI BP 3133 EP 3153 DI 10.4155/bio.14.278 PG 21 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8QP UT WOS:000349186300009 PM 25529882 ER PT J AU Johnson, N Dudbridge, F Orr, N Gibson, L Jones, ME Schoemaker, MJ Folkerd, EJ Haynes, BP Hopper, JL Southey, MC Dite, GS Apicella, C Schmidt, MK Broeks, A Van't Veer, LJ Atsma, F Muir, K Lophatananon, A Fasching, PA Beckmann, MW Ekici, AB Renner, SP Sawyer, E Tomlinson, I Kerin, M Miller, N Burwinkel, B Marme, F Schneeweiss, A Sohn, C Guenel, P Truong, T Cordina, E Menegaux, F Bojesen, SE Nordestgaard, BG Flyger, H Milne, R Zamora, MP Perez, JIA Benitez, J Bernstein, L Anton-Culver, H Ziogas, A Dur, CC Brenner, H Muller, H Arndt, V Dieffenbach, AK Meindl, A Heil, J Bartram, CR Schmutzler, RK Brauch, H Justenhoven, C Ko, YD Nevanlinna, H Muranen, TA Aittomaki, K Blomqvist, C Matsuo, K Dork, T Bogdanova, NV Antonenkova, NN Lindblom, A Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Chenevix-Trench, G Beesley, J Wu, AH Van den Berg, D Tseng, CC Lambrechts, D Smeets, D Neven, P Wildiers, H Chang-Claude, J Rudolph, A Nickels, S Flesch-Janys, D Radice, P Peterlongo, P Bonanni, B Pensotti, V Couch, FJ Olson, JE Wang, XS Fredericksen, Z Pankratz, VS Giles, GG Severi, G Baglietto, L Haiman, C Simard, J Goldberg, MS Labreche, F Dumont, M Soucy, P Teo, S Yip, CH Phuah, SY Cornes, BK Kristensen, VN Alnaes, GG Borresen-Dale, AL Zheng, W Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Andrulis, IL Knight, JA Glendon, G Mulligan, AM Devillee, P Figueroa, J Chanock, SJ Lissowska, J Sherman, ME Hall, P Schoof, N Hooning, M Hollestelle, A Oldenburg, RA Tilanus-Linthorst, M Liu, JJ Cox, A Brock, IW Reed, MWR Cross, SS Blot, W Signorello, LB Pharoah, PDP Dunning, AM Shah, M Kang, D Noh, DY Park, SK Choi, JY Hartman, M Miao, H Lim, WY Tang, A Hamann, U Forsti, A Rudiger, T Ulmer, HU Jakubowska, A Lubinski, J Jaworska-Bieniek, K Durda, K Sangrajrang, S Gaborieau, V Brennan, P Mckay, J Slager, S Toland, AE Vachon, C Yannoukakos, D Shen, CY Yu, JC Huang, CS Hou, MF Gonzalez-Neira, A Tessier, DC Vincent, D Bacot, F Luccarini, C Dennis, J Michailidou, K Bolla, MK Wang, J Easton, DF Garcia-Closas, M Dowsett, M Ashworth, A Swerdlow, AJ Peto, J Silva, ID Fletcher, O AF Johnson, Nichola Dudbridge, Frank Orr, Nick Gibson, Lorna Jones, Michael E. Schoemaker, Minouk J. Folkerd, Elizabeth J. Haynes, Ben P. Hopper, John L. Southey, Melissa C. Dite, Gillian S. Apicella, Carmel Schmidt, Marjanka K. Broeks, Annegien Van't Veer, Laura J. Atsma, Femke Muir, Kenneth Lophatananon, Artitaya Fasching, Peter A. Beckmann, Matthias W. Ekici, Arif B. Renner, Stefan P. Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Burwinkel, Barbara Marme, Frederik Schneeweiss, Andreas Sohn, Christof Guenel, Pascal Truong, Therese Cordina, Emilie Menegaux, Florence Bojesen, Stig E. Nordestgaard, Borge G. Flyger, Henrik Milne, Roger Zamora, M. Pilar Arias Perez, Jose Ignacio Benitez, Javier Bernstein, Leslie Anton-Culver, Hoda Ziogas, Argyrios Dur, Christina Clarke Brenner, Hermann Mueller, Heiko Arndt, Volker Dieffenbach, Aida Karina Meindl, Alfons Heil, Joerg Bartram, Claus R. Schmutzler, Rita K. Brauch, Hiltrud Justenhoven, Christina Ko, Yon-Dschun Nevanlinna, Heli Muranen, Taru A. Aittomaeki, Kristiina Blomqvist, Carl Matsuo, Keitaro Doerk, Thilo Bogdanova, Natalia V. Antonenkova, Natalia N. Lindblom, Annika Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Chenevix-Trench, Georgia Beesley, Jonathan Wu, Anna H. Van den Berg, David Tseng, Chiu-Chen Lambrechts, Diether Smeets, Dominiek Neven, Patrick Wildiers, Hans Chang-Claude, Jenny Rudolph, Anja Nickels, Stefan Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Bonanni, Bernardo Pensotti, Valeria Couch, Fergus J. Olson, Janet E. Wang, Xianshu Fredericksen, Zachary Pankratz, Vernon S. Giles, Graham G. Severi, Gianluca Baglietto, Laura Haiman, Chris Simard, Jacques Goldberg, Mark S. Labreche, France Dumont, Martine Soucy, Penny Teo, Soo Yip, Cheng Har Phuah, Sze Yee Cornes, Belinda K. Kristensen, Vessela N. Alnaes, Grethe Grenaker Borresen-Dale, Anne-Lise Zheng, Wei Winqvist, Robert Pylkaes, Katri Jukkola-Vuorinen, Arja Grip, Mervi Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Devillee, Peter Figueroa, Jonine Chanock, Stephen J. Lissowska, Jolanta Sherman, Mark E. Hall, Per Schoof, Nils Hooning, Maartje Hollestelle, Antoinette Oldenburg, Rogier A. Tilanus-Linthorst, Madeleine Liu, Jianjun Cox, Angie Brock, Ian W. Reed, Malcolm W. R. Cross, Simon S. Blot, William Signorello, Lisa B. Pharoah, Paul D. P. Dunning, Alison M. Shah, Mitul Kang, Daehee Noh, Dong-Young Park, Sue K. Choi, Ji-Yeob Hartman, Mikael Miao, Hui Lim, Wei Yen Tang, Anthony Hamann, Ute Foersti, Asta Ruediger, Thomas Ulmer, Hans Ulrich Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul Mckay, James Slager, Susan Toland, Amanda E. Vachon, Celine Yannoukakos, Drakoulis Shen, Chen-Yang Yu, Jyh-Cherng Huang, Chiun-Sheng Hou, Ming-Feng Gonzalez-Neira, Anna Tessier, Daniel C. Vincent, Daniel Bacot, Francois Luccarini, Craig Dennis, Joe Michailidou, Kyriaki Bolla, Manjeet K. Wang, Jean Easton, Douglas F. Garcia-Closas, Montserrat Dowsett, Mitch Ashworth, Alan Swerdlow, Anthony J. Peto, Julian Silva, Isabel dos Santos Fletcher, Olivia CA Gene Environm Interaction & Breast KConFab Investigators Australian Ovarian Canc Study Grp TI Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SEX-HORMONE LEVELS; PREMENOPAUSAL WOMEN; STEROID-HORMONES; SERUM; TWINS; ESTRADIOL; LOCI AB Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age <= 50 years. Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P-trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P-trend = 0.005) but not cases (P-trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P-het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age >= 15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P-trend = 0.002) but not for those who had their menarche age <= 11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P-trend = 0.29). Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels. C1 [Johnson, Nichola; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Johnson, Nichola; Orr, Nick] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Dudbridge, Frank; Gibson, Lorna] London Sch Hyg & Trop Med, Non Commun Dis Epidemiol Dept, London WC1E 7HT, England. [Jones, Michael E.; Schoemaker, Minouk J.] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Folkerd, Elizabeth J.; Haynes, Ben P.] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. [Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Dept, Melbourne, Vic 3010, Australia. [Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, NL-1066 CX Amsterdam, Netherlands. [Atsma, Femke] Radboud Univ Nijmegen, Sanquin, NL-6525 GA Nijmegen, Netherlands. [Muir, Kenneth; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AJ, W Midlands, England. [Fasching, Peter A.; Beckmann, Matthias W.; Renner, Stefan P.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, D-91012 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Ekici, Arif B.] Alexander Univ Erlangen, Inst Human Genet, D-91054 Erlangen, Germany. [Sawyer, Elinor] Guys Hosp, NIHR Comprehens Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, Kings Coll London,Div Canc Studies, London SE1 9RT, England. [Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Churchill Hosp, Oxford OX3 7LE, England. [Kerin, Michael; Miller, Nicola] Galway Univ Hosp, Inst Clin Sci, Galway, Ireland. [Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Heil, Joerg] Natl Univ Ireland, Galway, Ireland. [Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, D-69115 Heidelberg, Germany. [Sohn, Christof] German Canc Res Ctr, Unit Mol Epidemiol C080, DKFZ, D-69120 Heidelberg, Germany. [Sohn, Christof] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [Guenel, Pascal; Truong, Therese; Cordina, Emilie; Menegaux, Florence] INSERM, Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018L, F-75654 Paris, France. [Guenel, Pascal; Truong, Therese; Cordina, Emilie; Menegaux, Florence] Univ Paris 11, UMRS 1018, F-75654 Paris, France. [Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. [Milne, Roger] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. [Zamora, M. Pilar] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain. [Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 107, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid 28029, Spain. [Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Madrid 28029, Spain. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA. [Dur, Christina Clarke] Canc Prevent Inst Calif, Fremont, CA 95438 USA. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker; Dieffenbach, Aida Karina] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69121 Heidelberg, Germany. [Brenner, Hermann; Dieffenbach, Aida Karina] German Canc Consortium DKTK, D-69121 Heidelberg, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Clin Gynecol & Obstet, D-81675 Munich, Germany. [Bartram, Claus R.] Heidelberg Univ, Inst Human Genet, D-69121 Heidelberg, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, D-50931 Cologne, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Robert Bosch Stiftung GmbH, Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70184 Stuttgart, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Univ Tubingen, D-72074 Tubingen, Germany. [Ko, Yon-Dschun] Evangel Kliniken Bonn GGmbH, Dept Internal Med, D-53113 Bonn, Germany. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, FIN-00029 Helsinki, Finland. [Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, FIN-00029 Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. [Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Chikusa Ku, Nagoya, Aichi 4648681, Japan. [Doerk, Thilo] Hannover Med Sch, Dept Obstet & Gynaecol, D-30625 Hannover, Germany. [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany. [Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Bioctr Kuopio, FI-70211 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, FI-70029 Kuopio, Finland. [Kataja, Vesa] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia. [Chenevix-Trench, Georgia; Beesley, Jonathan] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Wu, Anna H.; Van den Berg, David; Tseng, Chiu-Chen] Univ Louvain, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium. [Lambrechts, Diether; Smeets, Dominiek; Haiman, Chris] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Lambrechts, Diether; Smeets, Dominiek] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Neven, Patrick; Wildiers, Hans] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiology Clin Canc Registry, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biomet & Epidemiol, D-20246 Hamburg, Germany. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Peterlongo, Paolo; Pensotti, Valeria] Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy. [Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Pensotti, Valeria] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Div Expt Pathol, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Olson, Janet E.; Fredericksen, Zachary; Pankratz, Vernon S.; Slager, Susan; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Simard, Jacques; Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. [Simard, Jacques; Goldberg, Mark S.] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. [Labreche, France] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ H3T 1A8, Canada. [Labreche, France] Univ Montreal, Dept Environm & Occupat Hlth Work, Montreal, PQ H3T 1A8, Canada. [Dumont, Martine; Soucy, Penny] Ctr Hosp Univ, Quebec Res Ctr, Can Genom Lab, Quebec City, PQ G1V 0A6, Canada. [Dumont, Martine; Soucy, Penny] Univ Laval, Quebec City, PQ G1V 0A6, Canada. [Teo, Soo; Yip, Cheng Har; Phuah, Sze Yee] Univ Malaya, Fac Med, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur 50603, Malaysia. [Teo, Soo; Phuah, Sze Yee] Sime Darby Med Ctr Subang Jaya, Canc Res Initiat Fdn, Subang Jaya 47500, Selangor Darul, Malaysia. [Cornes, Belinda K.] Natl Univ Singapore, Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore. [Kristensen, Vessela N.; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Kristensen, Vessela N.; Alnaes, Grethe Grenaker; Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Fac Div Ahus, N-0372 Oslo, Norway. [Zheng, Wei; Blot, William] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA. [Winqvist, Robert; Pylkaes, Katri] Univ Oulu, Oulu Univ Hosp, Dept Clin Chem & Bioctr Oulu, Lab Canc Genet & Tumor Biol, SF-90220 Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, SF-90220 Oulu, Finland. [Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, SF-90220 Oulu, Finland. [Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. [Glendon, Gord] Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Toronto, ON M5G 2C4, Canada. [Devillee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands. [Devillee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZC Leiden, Netherlands. [Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Hall, Per; Schoof, Nils] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Hooning, Maartje] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. [Hollestelle, Antoinette] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. [Oldenburg, Rogier A.; Tilanus-Linthorst, Madeleine] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Clin Genet, NL-3075 EA Rotterdam, Netherlands. [Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore. [Cox, Angie; Brock, Ian W.] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Inst Canc Studies, Sheffield S10 2HQ, S Yorkshire, England. [Reed, Malcolm W. R.] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Acad Unit Surg Oncol, Sheffield S10 2HQ, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England. [Blot, William] Int Epidemiol Inst, Rockville, MD 20850 USA. [Signorello, Lisa B.; Miao, Hui] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Signorello, Lisa B.; Miao, Hui] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England. [Shah, Mitul; Kang, Daehee; Noh, Dong-Young; Choi, Ji-Yeob] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea. [Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Park, Sue K.] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 110799, South Korea. [Park, Sue K.] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea. [Hartman, Mikael] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 119228, Singapore. [Hartman, Mikael; Lim, Wei Yen] Natl Univ Hlth Syst, Singapore 119228, Singapore. [Hartman, Mikael; Lim, Wei Yen] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore. [Tang, Anthony] Natl Univ Hlth Syst, Div Gen Surg, Singapore 119228, Singapore. [Hamann, Ute] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Foersti, Asta] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany. [Foersti, Asta] Lund Univ, Ctr Primary Hlth Care Res, SE-22100 Malmo, Sweden. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany. [Ulmer, Hans Ulrich] Frauenklin Stadtklin Baden Baden, D-76532 Baden, Switzerland. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, PL-70204 Szczecin, Poland. [Jaworska-Bieniek, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, PL-02091 Warsaw, Poland. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand. [Gaborieau, Valerie] Int Agcy Res Canc, F-69372 Lyon 08, France. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens 15310, Greece. [Shen, Chen-Yang] China Med Univ, Coll Publ Hlth, Taichung 40402, Taiwan. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. [Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei 114, Taiwan. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Dept Surg, Taipei 10048, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Ctr Canc, Kaohsiung 807, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Surg, Kaohsiung 807, Taiwan. [Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. [Dennis, Joe; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Jean; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. RP Johnson, N (reprint author), Inst Canc Res, Breakthrough Breast Canc Res Ctr, 237 Fulham Rd, London SW3 6JB, England. EM nichola.johnson@icr.ac.uk RI Gonzalez-Neira, Anna/C-5791-2015; Hartman, Mikael/B-4324-2011; Yip, Cheng-Har/B-1909-2010; Teo, Soo-hwang/H-2353-2014; Hartikainen, Jaana/E-6256-2015; Garcia-Closas, Montserrat /F-3871-2015; Atsma, F./L-4178-2015; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Renner, Stefan/F-1158-2014; Brenner, Hermann/B-4627-2017 OI Schoemaker, Minouk/0000-0001-8403-2234; Nevanlinna, Heli/0000-0002-0916-2976; Huang, Chiun-Sheng/0000-0002-6557-211X; Cross, Simon/0000-0003-2044-1754; Dunning, Alison Margaret/0000-0001-6651-7166; Heil, Joerg/0000-0002-4684-9099; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510; Giles, Graham/0000-0003-4946-9099; Dobrovic, Alexander/0000-0003-3414-112X; Arias Perez, Jose Ignacio/0000-0003-4500-397X; Garcia-Closas, Montserrat /0000-0003-1033-2650; Dite, Gillian/0000-0002-2448-2548; Bowtell, David/0000-0001-9089-7525; Renner, Stefan/0000-0003-2057-1268; Brenner, Hermann/0000-0002-6129-1572 FU Canadian Institutes of Health Research [CRN-87521]; Cancer Research UK [10124, C1287/A10118, C1287/A12014, C490/A10124, C8197/A10123]; Department of Health [, 03/DHCS/03/G121/51, NF-SI-0512-10122]; Intramural NIH HHS; Medical Research Council [MR/K006215/1]; NCI NIH HHS [CA098758, 5U01CA098216-07, CA116167, CA116201, CA128978, CA132839, CA54281, CA63464, N01CN25403, P30 CA68485, P50 CA116201, R01 CA077398, R01 CA092447, R01 CA77398, R01CA100374, R01CA148667, R01CA64277, R37CA70867, RFA-CA-06-503, U01 CA116167, U01 CA69417, U01 CA69467, U01 CA69638]; Wellcome Trust [090532]; Associazione Italiana per la Ricerca sul Cancro NR 24 TC 4 Z9 5 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 3 AR R51 DI 10.1186/bcr3662 PG 13 WC Oncology SC Oncology GA CA7FT UT WOS:000349083900007 PM 24887515 ER PT J AU Sato, M Kadota, M Tang, B Yang, HH Yang, YA Shan, M Weng, J Welsh, MA Flanders, KC Nagano, Y Michalowski, AM Clifford, RJ Lee, MP Wakefield, LM AF Sato, Misako Kadota, Mitsutaka Tang, Binwu Yang, Howard H. Yang, Yu-an Shan, Mengge Weng, Jia Welsh, Michael A. Flanders, Kathleen C. Nagano, Yoshiko Michalowski, Aleksandra M. Clifford, Robert J. Lee, Maxwell P. Wakefield, Lalage M. TI An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-beta in human breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION SIGNATURE; TGF-BETA; SIGNALING PATHWAY; CARCINOMA-CELLS; EPHA RECEPTOR; SMAD PROTEINS; MCF10AT CELLS; PROGRESSION; METASTASIS AB Introduction: Transforming growth factor-beta s (TGF-beta s) play a dual role in breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects. TGF-beta antagonists are showing promise in early-phase clinical oncology trials to neutralize the pro-oncogenic effects. However, there is currently no way to determine whether the tumor-suppressive effects of TGF-beta are still active in human breast tumors at the time of surgery and treatment, a situation that could lead to adverse therapeutic responses. Methods: Using a breast cancer progression model that exemplifies the dual role of TGF-beta, promoter-wide chromatin immunoprecipitation and transcriptomic approaches were applied to identify a core set of TGF-beta-regulated genes that specifically reflect only the tumor-suppressor arm of the pathway. The clinical significance of this signature and the underlying biology were investigated using bioinformatic analyses in clinical breast cancer datasets, and knockdown validation approaches in tumor xenografts. Results: TGF-beta-driven tumor suppression was highly dependent on Smad3, and Smad3 target genes that were specifically enriched for involvement in tumor suppression were identified. Patterns of Smad3 binding reflected the preexisting active chromatin landscape, and target genes were frequently regulated in opposite directions in vitro and in vivo, highlighting the strong contextuality of TGF-beta action. An in vivo-weighted TGF-beta/Smad3 tumor-suppressor signature was associated with good outcome in estrogen receptor-positive breast cancer cohorts. TGF-beta/Smad3 effects on cell proliferation, differentiation and ephrin signaling contributed to the observed tumor suppression. Conclusions: Tumor-suppressive effects of TGF-beta persist in some breast cancer patients at the time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo genomic approaches can identify such patients for exclusion from treatment with TGF-beta antagonists. C1 [Sato, Misako; Tang, Binwu; Yang, Yu-an; Shan, Mengge; Weng, Jia; Welsh, Michael A.; Flanders, Kathleen C.; Nagano, Yoshiko; Michalowski, Aleksandra M.; Wakefield, Lalage M.] Natl Canc Inst, Ctr Canc Res, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Kadota, Mitsutaka; Yang, Howard H.; Clifford, Robert J.; Lee, Maxwell P.] NCI, Ctr Canc Res, Lab Populat Genet, Bethesda, MD 20892 USA. [Sato, Misako] Osaka City Univ, Grad Sch Med, Dept Hepatol, Abeno Ku, Osaka 5458585, Japan. [Kadota, Mitsutaka] RIKEN, Ctr Dev Biol, Genome Resource & Anal Unit, Kobe, Hyogo 6500047, Japan. [Nagano, Yoshiko] Tokyo Med & Dent Univ, Dept Immunotherapeut, Bunkyo Ku, Tokyo 1138519, Japan. [Clifford, Robert J.] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. RP Wakefield, LM (reprint author), Natl Canc Inst, Ctr Canc Res, Lab Canc Biol & Genet, 37 Convent Dr, Bethesda, MD 20892 USA. EM lw34g@nih.gov FU Japan Society for the Promotion of Sciences Fellowships; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research [ZIA BC 005785] FX The authors thank Drs. Kent Hunter, Glenn Merlino, Stuart Yuspa and Tsutomu Matsubara for critical reading of the manuscript and helpful discussions, Dr. Xaolin Wu for performing the microarrays, and Anthony Vieira for help with the animal studies. Misako Sato and Yoshiko Nagano were supported by the Japan Society for the Promotion of Sciences Fellowships. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research ZIA BC 005785 (LMW). NR 86 TC 4 Z9 4 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 3 AR R57 DI 10.1186/bcr3668 PG 23 WC Oncology SC Oncology GA CA7FT UT WOS:000349083900013 PM 24890385 ER PT J AU Vazquez-Ortiz, G Chisholm, C Xu, XL Lahusen, TJ Li, CL Sakamuru, S Huang, RL Thomas, CJ Xia, MH Deng, CX AF Vazquez-Ortiz, Guelaguetza Chisholm, Cristine Xu, Xiaoling Lahusen, Tyler J. Li, Cuiling Sakamuru, Srilatha Huang, Ruili Thomas, Craig J. Xia, Menghang Deng, Chuxia TI Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells SO BREAST CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BASE EXCISION-REPAIR; POLY(ADP-RIBOSE) POLYMERASE; SUSCEPTIBILITY GENES; MUTATION CARRIERS; PARP INHIBITORS; OVARIAN-CANCER; IN-VITRO; BRCA1; TUMORS AB Introduction: Breast cancer is a devastating disease that results in approximately 40,000 deaths each year in the USA. Current drug screening and chemopreventatitive methods are suboptimal, due in part to the poor specificity of compounds for cancer cells. Poly (ADP-ribose) polymerase 1 (PARP1) inhibitor (PARPi)-mediated therapy is a promising approach for familial breast cancers caused by mutations of breast cancer-associated gene-1 and -2 (BRCA1/2), yet drug resistance frequently occurs during the treatment. Moreover, PARPis exhibit very little effect on cancers that are proficient for DNA repair and clinical efficacy for PARPis as single-agent therapies has yet to be illustrated. Methods: Using a quantitative high-throughput screening approach, we screened a library containing 2,816 drugs, most of which are approved for human or animal use by the Food and Drug Administration (FDA) or other countries, to identify compounds that sensitize breast cancer cells to PARPi. After initial screening, we performed further cellular and molecular analysis on lestaurtinib, which is an orally bioavailable multikinase inhibitor and has been used in clinical trials for myeloproliferative disorders and acute myelogenous leukemia. Results: Our study indicated that lestaurtinib is highly potent against breast cancers as a mono-treatment agent. It also strongly enhanced the activity of the potent PARPi AG14361 on breast cancer cell growth both in vitro and in vivo conditions. The inhibition of cancer growth is measured by increased apoptosis and reduced cell proliferation. Consistent with this, the treatment results in activation of caspase 3/7, and accumulation of cells in the G2 phase of the cell cycle, irrespective of their BRCA1 status. Finally, we demonstrated that AG14361 inhibits NF-kappa B signaling, which is further enhanced by lestaurtinib treatment. Conclusions: Lestaurtinib amplifies the ability of the PARP1 inhibitor AG14361 to kill BRCA1 mutant and wild-type breast cancer cells, at least in part, by inhibiting NF-kappa B signaling. Each of these drugs has been approved for clinical trials for several different cancers, thus, their combination treatment should be applicable for a breast cancer trial in the future. C1 [Vazquez-Ortiz, Guelaguetza; Chisholm, Cristine; Xu, Xiaoling; Lahusen, Tyler J.; Li, Cuiling; Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Sakamuru, Srilatha; Huang, Ruili; Thomas, Craig J.; Xia, Menghang] Natl Ctr Adv Translat Sci, NIH, Chem Genom Ctr, Rockville, MD 20850 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM chuxiad@mail.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We gratefully acknowledge the critical reading and helpful discussion of members of the Deng laboratory. This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 60 TC 3 Z9 3 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 3 AR R67 DI 10.1186/bcr3682 PG 14 WC Oncology SC Oncology GA CA7FT UT WOS:000349083900023 PM 24962108 ER PT J AU Xu, XH Hicks, C Li, Y Su, JW Shiloach, J Kaufman, JB Fitz, Y Eichacker, PQ Cui, XZ AF Xu, Xinhui Hicks, Caitlin Li, Yan Su, Junwu Shiloach, Joseph Kaufman, Jeanne B. Fitz, Yvonne Eichacker, Peter Q. Cui, Xizhong TI Purified cell wall from the probiotic bacterium Lactobacillus gasseri activates systemic inflammation and, at higher doses, produces lethality in a rat model SO CRITICAL CARE LA English DT Article ID ORGAN DYSFUNCTION SYNDROME; PLACEBO-CONTROLLED TRIAL; LACTIC-ACID BACTERIA; HUMAN-MONOCYTES; PEPTIDOGLYCAN; ADHESION; GUT; INFECTION; CYTOKINE; RELEASE AB Introduction: One proposed benefit of probiotic therapy is that probiotic bacterial cell-wall binding to intestinal cell pathogen-recognition receptors activates protective innate immunity. However, in critically ill patients, intestinal epithelium disruption by shock or other insults may compromise this compartmentalized response and cause systemic bacteria and cell-wall translocation. The effects of intravascular introduction of probiotic bacterial cell wall are unclear. Methods: We investigated 24-hour infusions of purified cell wall from Lactobacillus gasseri ATC33323 (L. gasseri), a probiotic bacterium, in Sprague Dawley rats (n = 49). Results: Increasing cell-wall doses (0 (control), 10, 20, 40, 80, or 160 mg/kg over 24 hours) produced dose-ordered decreases in survival measured after 168 hours (11 survivors/11 total (100%), seven of seven (100%), seven of seven (100%), six of eight (75%), five of eight (63%), and one of nine (11%), respectively, P<0.0001). The L. gasseri cell wall was equally or more lethal than Staphylococcus aureus cell wall, which was previously studied (100% to 88% survival with the same increasing doses). During challenge, compared with controls, L. gasseri cell wall produced increases in blood IL-1 beta, IL-10, tumor necrosis factor-a, migratory inhibitory protein-la, monocyte chemotactic protein-1, and nitric oxide, and decreases in neutrophils, lymphocytes, and platelets that were greater with higher versus lower doses (P <= 0.05). Medium-dose cell wall (40 and 80 mg/kg combined) progressively decreased blood pressure and increased heart rate, and all doses increased lactate, hepatic transaminases, and creatinine phosphokinase (P <= 0.05). Conclusion: Although L. gasseri, like other probiotic bacteria, is considered safe, its cell wall can stimulate the maladaptive inflammatory response associated with pathogenic bacteria. Such effects deserve study, especially regarding critically ill patients. C1 [Xu, Xinhui; Hicks, Caitlin; Li, Yan; Su, Junwu; Fitz, Yvonne; Eichacker, Peter Q.; Cui, Xizhong] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Shiloach, Joseph; Kaufman, Jeanne B.] NIDDK, NIH, Bethesda, MD 20892 USA. [Xu, Xinhui] Shanghai Jiao Tong Univ, Dept Crit Care Med, Renji Hosp, Sch Med, Shanghai 200030, Peoples R China. RP Cui, XZ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM cxizhong@mail.cc.nih.gov NR 38 TC 1 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 4 AR R140 DI 10.1186/cc13966 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CA4MJ UT WOS:000348878200024 PM 24989885 ER PT J AU Pniewska, E Sokolowska, M Kuprys-Lipinska, I Kacprzak, D Kuna, P Pawliczak, R AF Pniewska, Ewa Sokolowska, Milena Kuprys-Lipinska, Izabela Kacprzak, Dorota Kuna, Piotr Pawliczak, Rafal TI Exacerbating Factors Induce Different Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Asthmatics, Patients with Chronic Obstructive Pulmonary Disease and Healthy Subjects SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Airway inflammation; Asthma; Chronic obstructive pulmonary disease; Exacerbating factors; House dust mites; Lipopolysaccharides; TaqMan low density array ID HOUSE-DUST MITE; CHITINASE-LIKE PROTEIN; SYSTEMIC INFLAMMATION; AIRWAY INFLAMMATION; PHOSPHOLIPASE A(2); ALLERGEN DER-P-1; DENDRITIC CELLS; DERMATOPHAGOIDES-PTERONYSSINUS; EPITHELIAL-CELLS; DOWN-REGULATION AB Background: Despite several common phenotypic features, chronic obstructive pulmonary disease (COPD) and severe asthma differ with regard to their causative factors and pathophysiology. Both diseases may be exacerbated by environmental factors, however, the molecular profiles of disease episodes have not been comprehensively studied. We identified differences in gene and protein expression profiles expressed by peripheral blood mononuclear cells (PBMC) of COPD patients, patients with atopic asthma and healthy subjects when challenged with exacerbating factors in vitro: lipopolysaccharide (LPS), house dust mite (HDM) and cat allergen. Methods: PBMC isolated from patients with severe atopic asthma and COPD, as well as healthy subjects were stimulated with rDer p 1 DG, rFel d 1 DG and LPS. The changes in the expression of 47 genes belonging to five groups (phospholipase A 2, eicosanoids, transcription factors, cytokines and airway remodeling) were studied using TaqMan low density array cards. Immunoblotting was used to study relative protein expression. Results: rDer p 1 significantly up-regulated the expression of PLA2G4A, PLA2G6, PLA2G15, CYSLTR1, LB4R2, PTGS1, PTGS2, FOXP1, GATA3, HDAC2, IREB2, PPARG, STAT4, TSLP and CHI3L1 genes in asthmatics in comparison to healthy subjects. LPS induced significant expression of ANXA1 and LTA4H in asthmatics when compared to COPD patients and healthy subjects. SOX6, STAT4 and IL1RL1 were induced in COPD after LPS stimulation. Analysis of protein expression revealed a pattern similar to mRNA expression. Conclusions: LPS-induced exacerbation of asthma and COPD is characterized by differential expression of selected genes in PBMC. HDM allergen changed the expression profile of inflammatory genes between patients with asthma of atopic origin and healthy controls. (C) 2015 S. Karger AG, Basel C1 [Pniewska, Ewa; Kacprzak, Dorota; Pawliczak, Rafal] Med Univ Lodz, Fac Biomed Sci & Postgrad, Div Allergol Immunol & Dermatol, Dept Immunopathol, Lodz, Poland. [Kuprys-Lipinska, Izabela; Kuna, Piotr] Med Univ Lodz, Dept Internal Dis Asthma & Allergy, Lodz, Poland. [Sokolowska, Milena] Natl Inst Hlth, Dept Crit Care Med, Bethesda, MD USA. RP Pawliczak, R (reprint author), Med Univ Lodz, Dept Immunopathol, 7-9 Zeligowskiego,Bldg 2,Room 122, Lodz, Poland. EM rafal.pawliczak@csk.umed.lodz.pl RI Pawliczak, Rafal/S-9649-2016 FU Medical University of Lodz grant [503/0-149-03/503-01]; [N N402 516939] FX Support for this paper was obtained from a science budget for years 2010-2013 as research project (N N402 516939) and a Medical University of Lodz grant (503/0-149-03/503-01). NR 71 TC 1 Z9 1 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 EI 1423-0097 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2014 VL 165 IS 4 BP 229 EP 243 DI 10.1159/000370067 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA CA9HM UT WOS:000349233000002 PM 25634111 ER PT J AU Ramachandran, R Jha, J Chattoraj, DK AF Ramachandran, Revathy Jha, Jyoti Chattoraj, Dhruba K. TI Chromosome Segregation in Vibrio cholerae SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE Bacterial mitosis; Divided genomes; Coordination of replication and segregation; Par-independent polar segregation ID ESCHERICHIA-COLI CHROMOSOME; SEPARATE CELL HALVES; REPLICATION ORIGIN REGIONS; BACILLUS-SUBTILIS; PLASMID PARTITION; E. COLI; MULTIPLE CHROMOSOMES; POLAR LOCALIZATION; DNA-REPLICATION; RNA-POLYMERASE AB The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae compare with those in other bacteria, and highlight some of the remaining questions regarding the process of bacterial chromosome segregation. (C) 2015 S. Karger AG, Basel C1 [Ramachandran, Revathy; Jha, Jyoti; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD USA. RP Chattoraj, DK (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD USA. EM chattoraj@nih.gov FU Intramural Research Program, Center for Cancer Research, The National Cancer Institute FX The authors are indebted to Christophe Possoz [David et al., 2014], Francois-Xavier Barre [Demarre et al., 2014] and Xavier De Bone [Deghelt et al., 2014] for communicating results prior to publication. The authors are also indebted to Abhishek Goel for help in drawing the figures, and to David Lane, Christophe Possoz, Anthony Vecchiarelli, Zemer Gitai, Michael Lichten and Michael Yarmolinsky for thoughtful comments, and Jemima Barrowman for editing the manuscript. This work was supported by the Intramural Research Program, Center for Cancer Research, The National Cancer Institute. NR 96 TC 0 Z9 1 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 EI 1660-2412 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2014 VL 24 IS 5-6 BP 360 EP 370 DI 10.1159/000368853 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA CB5HE UT WOS:000349657300006 PM 25732338 ER PT J AU Simpkin, A Cochran, E Cameron, F Dattani, M de Bock, M Dunger, DB Forsander, G Guran, T Harris, J Isaac, I Hussain, K Kleta, R Peters, C Tasic, V Williams, R Peng, FYK O'Rahilly, S Gorden, P Semple, RK Bockenhauer, D AF Simpkin, Arabella Cochran, Elaine Cameron, Fergus Dattani, Mehul de Bock, Martin Dunger, David B. Forsander, Gun Guran, Tulay Harris, Julie Isaac, Iona Hussain, Khalid Kleta, Robert Peters, Catherine Tasic, Velibor Williams, Rachel Peng, Fabian Yap Kok O'Rahilly, Stephen Gorden, Philipp Semple, Robert K. Bockenhauer, Detlef TI Insulin Receptor and the Kidney: Nephrocalcinosis in Patients with Recessive INSR Mutations SO NEPHRON PHYSIOLOGY LA English DT Article ID RABSON-MENDENHALL SYNDROME; MEDULLARY SPONGE KIDNEY; DONOHUE-SYNDROME; TUBULAR DYSFUNCTION; DIABETES-MELLITUS; CONVOLUTED TUBULE; GENE; LEPRECHAUNISM; RESISTANCE; DELETION AB Background/Aims: Donohue and Rabson-Mendenhall syndrome are rare autosomal recessive disorders caused by mutations in the insulin receptor gene, INSR. Phenotypic features include extreme insulin resistance, linear growth retardation, paucity of fat and muscle, and soft tissue overgrowth. The insulin receptor is also expressed in the kidney, where animal data suggest it plays a role in glomerular function and blood pressure (BP) regulation, yet such a role in the human kidney is untested. Patients with biallelic INSR mutations provide a rare opportunity to ascertain its role in man. Methods: Retrospective review of patients with INSR mutations. Data for BP, renal imaging, plasma creatinine and electrolyte levels, as well as urine protein, albumin and calcium excretion were sought from the treating clinicians. Results: From 33 patients with INSR mutations, data were available for 17 patients. Plasma creatinine was low (mean +/- SD: 25 +/- 9 mu mol/l) and mean plasma electrolyte concentrations were within the normal range (n = 13). Systolic BP ranged between the 18th and 91st percentile for age, sex, height and weight (n = 9; mean +/- SD: 49 +/- 24). Twenty-four-hour urinary calcium data were available from 10 patients and revealed hyper-calciuria in all (mean +/- SD: 0.32 +/- 0.17 mmol/kg/day; normal < 0.1). Nephrocalcinosis was present in all patients (n = 17). Urinary albumin excretion (n = 7) ranged from 4.3-122.5 mu g/min (mean +/- SD: 32.4 +/- 41.0 mu g/min; normal <20). Conclusions: INSR dysfunction is associated with hypercalciuria and nephrocalcinosis. No other consistent abnormality of renal function was noted. Normotension and stable glomerular function with only moderate proteinuria is in contrast to genetically modified mice who have elevated BP and progressive diabetic nephropathy. (C) 2014 S. Karger AG, Basel C1 [Simpkin, Arabella; Dattani, Mehul; Hussain, Khalid; Kleta, Robert; Peters, Catherine; Bockenhauer, Detlef] UCL Inst Child Hlth, London, England. [Simpkin, Arabella; Dattani, Mehul; Hussain, Khalid; Kleta, Robert; Peters, Catherine; Bockenhauer, Detlef] Great Ormond St Hosp Children NHS Fdn Trust, London, England. [Cochran, Elaine; Gorden, Philipp] NIDDK, Diabet Endocrine & Obes Branch, Bethesda, MD 20892 USA. [Cameron, Fergus] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [de Bock, Martin] Univ Auckland, Liggins Inst, Auckland 1, New Zealand. [Harris, Julie; Isaac, Iona; O'Rahilly, Stephen; Semple, Robert K.] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England. [Dunger, David B.; Williams, Rachel] Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England. [Forsander, Gun] Sahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Gothenburg, Sweden. [Guran, Tulay] Marmara Univ Hosp, Istanbul, Turkey. [Harris, Julie; Isaac, Iona; O'Rahilly, Stephen; Semple, Robert K.] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metab Res Labs, Cambridge, England. [Tasic, Velibor] Univ Childrens Hosp, Dept Pediat Nephrol, Sch Med, Skopje, Macedonia. [Peng, Fabian Yap Kok] KK Womens & Childrens Hosp, Singapore, Singapore. RP Bockenhauer, D (reprint author), Inst Child Hlth, 30 Guilford St, London WC1N 3EH, England. EM d.bockenhauer@ucl.ac.uk OI Forsander, Gun A/0000-0002-0266-9651; Simpkin, Arabella/0000-0001-6652-8789; Yap, Fabian/0000-0003-1083-7958; Semple, Robert/0000-0001-6539-3069 FU European Union, FP7 [2012-305608]; Wellcome Trust [WT098498, WT095515]; Medical Research Council Centre for Obesity and Related Disorders; United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre FX D.B. is a HEFCE Clinical Reader. Funding for this study was kindly provided by the European Union, FP7 [grant agreement 2012-305608 'European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics)' to R.K. and D.B.]. R.K.S. and S.O. were supported by the Wellcome Trust (grants WT098498 and WT095515, respectively), the Medical Research Council Centre for Obesity and Related Disorders, and the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. NR 32 TC 3 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2137 J9 NEPHRON PHYSIOL JI Nephron Physiol. PY 2014 VL 128 IS 3-4 BP 55 EP 61 DI 10.1159/000366225 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CB1BQ UT WOS:000349361900002 ER PT B AU Fleisher, TA AF Fleisher, Thomas A. BE Etzioni, A Ochs, HD TI Immunological Tests - from the Microscope to Whole Genome Analysis SO PRIMARY IMMUNODEFICIENCY DISORDERS: A HISTORIC AND SCIENTIFIC PERSPECTIVE LA English DT Article; Book Chapter ID CHRONIC GRANULOMATOUS-DISEASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; SEVERE COMBINED IMMUNODEFICIENCY; MEDIATED CYTOTOXICITY; FLOW-CYTOMETRY; INFECTIONS; DEFICIENCY; CELLS; SERUM; IDENTIFICATION C1 NIH, Dept Lab Med, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, NIH Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 62 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411554-5; 978-0-12-407179-7 PY 2014 BP 51 EP 63 PG 13 WC History & Philosophy Of Science; Immunology SC History & Philosophy of Science; Immunology GA BB9QC UT WOS:000348561100007 ER PT B AU Holland, SM AF Holland, Steven M. BE Etzioni, A Ochs, HD TI Chronic Granulomatous Disease - from a Fatal Disease to a Curable One SO PRIMARY IMMUNODEFICIENCY DISORDERS: A HISTORIC AND SCIENTIFIC PERSPECTIVE LA English DT Article; Book Chapter ID RESPIRATORY BURST OXIDASE; NEUTROPHIL CYTOCHROME-B; CELL-FREE SYSTEM; PATHOGEN GRANULIBACTER-BETHESDENSIS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; DEPENDENT SUPEROXIDE-PRODUCTION; DISCOID LUPUS-ERYTHEMATOSUS; FUNCTIONAL NADPH OXIDASE; INTERFERON-GAMMA; CORTICOSTEROID-THERAPY C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 133 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411554-5; 978-0-12-407179-7 PY 2014 BP 152 EP 171 PG 20 WC History & Philosophy Of Science; Immunology SC History & Philosophy of Science; Immunology GA BB9QC UT WOS:000348561100015 ER PT B AU Leonard, WJ AF Leonard, Warren J. BE Etzioni, A Ochs, HD TI Severe Combined Immunodeficiency as Diseases of Defective Cytokine Signaling SO PRIMARY IMMUNODEFICIENCY DISORDERS: A HISTORIC AND SCIENTIFIC PERSPECTIVE LA English DT Article; Book Chapter ID INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; X-CHROMOSOME INACTIVATION; B-CELL DIFFERENTIATION; NATURAL-KILLER-CELLS; RECEPTOR BETA-CHAIN; IL-2 RECEPTOR; T-CELLS; ALPHA-CHAIN; CUTTING EDGE; GENE-THERAPY C1 [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 93 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411554-5; 978-0-12-407179-7 PY 2014 BP 182 EP 197 PG 16 WC History & Philosophy Of Science; Immunology SC History & Philosophy of Science; Immunology GA BB9QC UT WOS:000348561100017 ER PT J AU Mattson, MP AF Mattson, Mark P. TI CHALLENGING ONESELF INTERMITTENTLY TO IMPROVE HEALTH SO DOSE-RESPONSE LA English DT Article DE brain function; exercise; hormesis; intermittent fasting ID DISEASE RISK MARKERS; GREEN TEA CATECHINS; CELL-CYCLE ARREST; DIETARY RESTRICTION; PHYSICAL-ACTIVITY; OXIDATIVE STRESS; KAPPA-B; MITOCHONDRIAL BIOGENESIS; CALORIE RESTRICTION; NEUROTROPHIC FACTOR AB Humans and their predecessors evolved in environments where they were challenged intermittently with: 1) food scarcity; 2) the need for aerobic fitness to catch/kill prey and avoid or repel attackers; and 3) exposure to biological toxins present in foodstuffs. Accordingly, cells and organ systems acquired and retained molecular signaling and metabolic pathways through which the environmental challenges enhanced the functionality and resilience of the cells and organisms. Within the past 60 years there has been a precipitous diminution of such challenges in modern societies because of the development of technologies that provide a continuous supply of energy-dense processed foods and that largely eliminate the need for physical exertion. As a consequence of the modern 'couch potato' lifestyle, signaling pathways that mediate beneficial effects of environmental challenges on health and disease resistance are disengaged, thereby rendering people vulnerable to obesity, diabetes, cardiovascular disease, cancers and neurodegenerative disorders. Reversal of the epidemic of diseases caused by unchallenging lifestyles will require a society-wide effort to re-introduce intermittent fasting, exercise and consumption of plants containing hormetic phytochemicals into daily and weekly routines. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov FU Intramural Research Program of the National Institute on Aging, NIH FX This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 127 TC 11 Z9 11 U1 4 U2 20 PU INT DOSE-RESPONSE SOC PI AMHERST PA UNIV MASSACHUSETTS SPH, MORRILL SCI CTR 1, N344, 639 N PLEASANT ST, AMHERST, MA 01003-9298 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PY 2014 VL 12 IS 4 BP 600 EP 618 DI 10.2203/dose-response.14-028.Mattson PG 19 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA AX0SN UT WOS:000346662400009 PM 25552960 ER PT J AU Zelner, JL Trostle, J Goldstick, JE Cevallos, W House, JS Eisenberg, JNS AF Zelner, Jonathan L. Trostle, James Goldstick, Jason E. Cevallos, William House, James S. Eisenberg, Joseph N. S. BA Choffnes, E.R. Mack, A BF Choffnes, E.R. Mack, A GP Inst Med TI SOCIAL CONNECTEDNESS CAN INHIBIT DISEASE TRANSMISSION: SOCIAL ORGANIZATION, COHESION, VILLAGE CONTEXT, AND INFECTION RISK IN RURAL ECUADOR SO INFLUENCE OF GLOBAL ENVIRONMENTAL CHANGE ON INFECTIOUS DISEASE DYNAMICS: WORKSHOP SUMMARY LA English DT Article; Book Chapter ID RANDOM-EFFECTS MODELS; NETWORKS; HEALTH; WATER; EPIDEMIOLOGY; SANITATION; COMMUNITY; DIARRHEA; BEHAVIOR; AIDS AB Social networks are typically seen as conduits for the spread of disease and disease risk factors. However, social relationships also reduce the incidence of chronic disease and potentially infectious diseases. Seldom are these opposing effects considered simultaneously. We have shown how and why diarrheal disease spreads more slowly to and in rural Ecuadorian villages that are more remote from the area's population center. Reduced contact with outside individuals partially accounts for remote villages' relatively lower prevalence of diarrheal disease. But equally or more important is the greater density of social ties between individuals in remote communities, which facilitates the spread of individual and collective practices that reduce the transmission of diarrheal disease. C1 [Zelner, Jonathan L.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Zelner, Jonathan L.] NIH, Res & Policy Infect Dis Dynam RAPIDD Program, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Trostle, James] Trinity Coll, Dept Anthropol, Hartford, CT 06016 USA. [Goldstick, Jason E.] Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Cevallos, William] Univ San Francisco Quito, Dept Microbiol, Quito, Ecuador. [House, James S.] Univ Michigan, Inst Social Res, Dept Sociol, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. [Eisenberg, Joseph N. S.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Zelner, JL (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. NR 31 TC 0 Z9 0 U1 2 U2 6 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-30499-3 PY 2014 BP 251 EP 266 PG 16 WC Environmental Sciences; Environmental Studies; Public, Environmental & Occupational Health; Infectious Diseases SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Infectious Diseases GA BB8KF UT WOS:000346766300012 ER PT J AU Bhatt, S Gething, PW Brady, OJ Messina, JP Farlow, AW Moyes, CL Drake, JM Brownstein, JS Hoen, AG Sankoh, O Myers, MF George, DB Jaenisch, T Wint, GRW Simmons, CP Scott, TW Farrar, JJ Hay, SI AF Bhatt, Samir Gething, Peter W. Brady, Oliver J. Messina, Jane P. Farlow, Andrew W. Moyes, Catherine L. Drake, John M. Brownstein, John S. Hoen, Anne G. Sankoh, Osman Myers, Monica F. George, Dylan B. Jaenisch, Thomas Wint, G. R. William Simmons, Cameron P. Scott, Thomas W. Farrar, Jeremy J. Hay, Simon I. BA Choffnes, E.R. Mack, A BF Choffnes, E.R. Mack, A GP Inst Med TI THE GLOBAL DISTRIBUTION AND BURDEN OF DENGUE SO INFLUENCE OF GLOBAL ENVIRONMENTAL CHANGE ON INFECTIOUS DISEASE DYNAMICS: WORKSHOP SUMMARY LA English DT Article; Book Chapter ID PLASMODIUM-FALCIPARUM ENDEMICITY; AEDES-AEGYPTI DIPTERA; LIFE TABLE MODEL; HEMORRHAGIC-FEVER; PSEUDO-ABSENCES; YELLOW-FEVER; DISEASE; TRANSMISSION; POPULATION; ALGORITHM AB Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes (Simmons et al., 2012). For some patients, dengue is a life-threatening illness (WHO, 2009). There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread (Tatem et al., 2006). The contemporary worldwide distribution of the risk of dengue virus infection (Brady et al., 2012) and its public health burden are poorly known (Halstead, 1988; WHO, 2009). Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of clinical or subclinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization (2009). Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation. C1 [Bhatt, Samir; Gething, Peter W.; Brady, Oliver J.; Messina, Jane P.; Farlow, Andrew W.; Moyes, Catherine L.; Drake, John M.; Myers, Monica F.; Wint, G. R. William; Scott, Thomas W.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Brady, Oliver J.] Oxitec Ltd, Abingdon OX14 4RX, Oxon, England. [Drake, John M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Brownstein, John S.; Farrar, Jeremy J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Brownstein, John S.; Farrar, Jeremy J.] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Hoen, Anne G.; Farrar, Jeremy J.] Dartmouth Coll, Dept Community & Family Med, Geisel Sch Med, Hanover, NH 03755 USA. [Sankoh, Osman] INDEPTH Network Secretariat, Accra, Ghana. [Sankoh, Osman] Univ Witwatersrand, Sch Publ Hlth, ZA-2000 Johannesburg, South Africa. [Sankoh, Osman] Heidelberg Univ, Inst Publ Hlth, D-69120 Heidelberg, Germany. [George, Dylan B.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Jaenisch, Thomas] Univ Heidelberg Hosp, Sect Clin Trop Med, Dept Infect Dis, D-69120 Heidelberg, Germany. [Wint, G. R. William] Univ Oxford, Dept Zool, Environm Res Grp Oxford ERGO, Oxford OX1 3PS, England. [Simmons, Cameron P.] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Simmons, Cameron P.] Univ Oxford, Ctr Trop Med, Churchill Hosp, Oxford OX3 7LJ, England. [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Farrar, Jeremy J.] Natl Univ Singapore, Dept Med, Singapore 119228, Singapore. RP Bhatt, S (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England. NR 53 TC 0 Z9 0 U1 1 U2 28 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-30499-3 PY 2014 BP 297 EP 310 PG 14 WC Environmental Sciences; Environmental Studies; Public, Environmental & Occupational Health; Infectious Diseases SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Infectious Diseases GA BB8KF UT WOS:000346766300015 ER PT J AU Basu, K Garnham, CP Nishimiya, Y Tsuda, S Braslavsky, I Davies, P AF Basu, Koli Garnham, Christopher P. Nishimiya, Yoshiyuki Tsuda, Sakae Braslavsky, Ido Davies, Peter TI Determining the Ice-binding Planes of Antifreeze Proteins by Fluorescence-based Ice Plane Affinity SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Chemistry; Issue 83; Materials; Life Sciences; Optics; antifreeze proteins; Ice adsorption; Fluorescent labeling; Ice lattice planes; ice-binding proteins; Single ice crystal ID POLAR FISHES; MECHANISM; GROWTH; ADSORPTION; PEPTIDES; CRYSTALS; ISOFORM; SITE; GLYCOPEPTIDES; HYPERACTIVITY AB Antifreeze proteins (AFPs) are expressed in a variety of cold-hardy organisms to prevent or slow internal ice growth. AFPs bind to specific planes of ice through their ice-binding surfaces. Fluorescence-based ice plane affinity (FIPA) analysis is a modified technique used to determine the ice planes to which the AFPs bind. FIPA is based on the original ice-etching method for determining AFP-bound ice-planes. It produces clearer images in a shortened experimental time. In FIPA analysis, AFPs are fluorescently labeled with a chimeric tag or a covalent dye then slowly incorporated into a macroscopic single ice crystal, which has been preformed into a hemisphere and oriented to determine the a-and c-axes. The AFP-bound ice hemisphere is imaged under UV light to visualize AFP-bound planes using filters to block out nonspecific light. Fluorescent labeling of the AFPs allows real-time monitoring of AFP adsorption into ice. The labels have been found not to influence the planes to which AFPs bind. FIPA analysis also introduces the option to bind more than one differently tagged AFP on the same single ice crystal to help differentiate their binding planes. These applications of FIPA are helping to advance our understanding of how AFPs bind to ice to halt its growth and why many AFP-producing organisms express multiple AFP isoforms. C1 [Basu, Koli; Davies, Peter] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada. [Garnham, Christopher P.] NINDS, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Nishimiya, Yoshiyuki; Tsuda, Sakae] Natl Inst Adv Ind Sci & Technol, Res Inst Genome Based Biofactory, Tokyo, Japan. [Braslavsky, Ido] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Inst Biochem Food Sci & Nutr, IL-91905 Jerusalem, Israel. RP Davies, P (reprint author), Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada. EM peter.davies@queensu.ca FU Canadian Institutes of Health Research; Japan Society for the Promotion of Science (JSPS) [23310171]; Japan Bio-oriented Technology Research Advancement Institution (BRAIN) FX PLD holds the Canada Research Chair in Protein Engineering. This work was funded by a grant from the Canadian Institutes of Health Research to PLD. This work was also supported by a Grant-in-Aid for scientific research from the Japan Society for the Promotion of Science (JSPS) (No. 23310171) and from the Japan Bio-oriented Technology Research Advancement Institution (BRAIN). We are grateful to Drs. Chris Marshall and Mike Kuiper for pioneering work that led to FIPA. We are also grateful to Dr. Sakae Tsuda for providing facilities for some of this work and to Dr. Laurie Graham for setting up the fluorescent light excitation and emission filters. NR 35 TC 2 Z9 2 U1 2 U2 19 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2014 IS 83 AR e51185 DI 10.3791/51185 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ9DZ UT WOS:000348513500059 PM 24457629 ER PT S AU Mansoor, A Bagci, U Mollura, DJ AF Mansoor, Awais Bagci, Ulas Mollura, Daniel J. BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI Optimally Stabilized PET Image Denoising Using Trilateral Filtering SO Medical Image Computing and Computer-Assisted Intervention - MICCAI 2014, Pt I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol DE Positron emission tomography; trilateral filtering; generalized variance stabilizing transformation; denoising ID EMISSION IMAGES AB Low-resolution and signal-dependent noise distribution in positron emission tomography (PET) images makes denoising process an inevitable step prior to qualitative and quantitative image analysis tasks. Conventional PET denoising methods either over-smooth small-sized structures due to resolution limitation or make incorrect assumptions about the noise characteristics. Therefore, clinically important quantitative information may be corrupted. To address these challenges, we introduced a novel approach to remove signal-dependent noise in the PET images where the noise distribution was considered as Poisson-Gaussian mixed. Meanwhile, the generalized Anscombe's transformation (GAT) was used to stabilize varying nature of the PET noise. Other than noise stabilization, it is also desirable for the noise removal filter to preserve the boundaries of the structures while smoothing the noisy regions. Indeed, it is important to avoid significant loss of quantitative information such as standard uptake value (SUV)-based metrics as well as metabolic lesion volume. To satisfy all these properties, we extended bilateral filtering method into trilateral filtering through multiscaling and optimal Gaussianization process. The proposed method was tested on more than 50 PET-CT images from various patients having different cancers and achieved the superior performance compared to the widely used denoising techniques in the literature. C1 [Mansoor, Awais; Bagci, Ulas; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Bagci, U (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ulas.bagci@nih.gov OI Bagci, Ulas/0000-0001-7379-6829 NR 12 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-10404-1; 978-3-319-10403-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8673 BP 130 EP 137 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC0GL UT WOS:000349019600017 ER PT S AU Irfanoglu, MO Modi, P Nayak, A Knutsen, A Sarlls, J Pierpaoli, C AF Irfanoglu, M. Okan Modi, Pooja Nayak, Amritha Knutsen, Andrew Sarlls, Joelle Pierpaoli, Carlo BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI DR-BUDDI: Diffeomorphic Registration for Blip Up-Down Diffusion Imaging SO Medical Image Computing and Computer-Assisted Intervention - MICCAI 2014, Pt I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol ID ECHO-PLANAR IMAGES; DISTORTION; BRAIN; FRAMEWORK AB In this work we propose a novel method to correct echo planar imaging (EPI) distortions in diffusion MRI data acquired with reversed phase encoding directions ("blip-up blip-down" acquisitions). The transformation model is symmetric, diffeomorphic and capable of capturing large deformations. It can take advantage of a structural MRI target and include the contribution of diffusion weighted images, in addition to EPI images acquired without diffusion sensitization. The proposed correction significantly outperform existing strategies, assuring anatomically accurate characterization of the orientation, mean diffusivity, and anisotropy of white matter structures in the human brain. C1 [Irfanoglu, M. Okan; Modi, Pooja; Nayak, Amritha; Knutsen, Andrew; Sarlls, Joelle; Pierpaoli, Carlo] NIH, Bethesda, MD 20892 USA. RP Irfanoglu, MO (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-10404-1; 978-3-319-10403-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8673 BP 218 EP 226 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC0GL UT WOS:000349019600028 ER PT S AU Roth, HR Lu, L Seff, A Cherry, KM Hoffman, J Wang, SJ Liu, JM Turkbey, E Summers, RM AF Roth, Holger R. Lu, Le Seff, Ari Cherry, Kevin M. Hoffman, Joanne Wang, Shijun Liu, Jiamin Turkbey, Evrim Summers, Ronald M. BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI A New 2.5D Representation for Lymph Node Detection Using Random Sets of Deep Convolutional Neural Network Observations SO Medical Image Computing and Computer-Assisted Intervention - MICCAI 2014, Pt I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol ID CT DATA; SEGMENTATION AB Automated Lymph Node (LN) detection is an important clinical diagnostic task but very challenging due to the low contrast of surrounding structures in Computed Tomography (CT) and to their varying sizes, poses, shapes and sparsely distributed locations. State-of-the-art studies show the performance range of 52.9% sensitivity at 3.1 false-positives per volume (FP/vol.), or 60.9% at 6.1 FP/vol. for mediastinal LN, by one-shot boosting on 3D HAAR features. In this paper, we first operate a preliminary candidate generation stage, towards similar to 100% sensitivity at the cost of high FP levels (similar to 40 per patient), to harvest volumes of interest (VOI). Our 2.5D approach consequently decomposes any 3D VOI by resampling 2D reformatted orthogonal views N times, via scale, random translations, and rotations with respect to the VOI centroid coordinates. These random views are then used to train a deep Convolutional Neural Network (CNN) classifier. In testing, the CNN is employed to assign LN probabilities for all N random views that can be simply averaged (as a set) to compute the final classification probability per VOI. We validate the approach on two datasets: 90 CT volumes with 388 mediastinal LNs and 86 patients with 595 abdominal LNs. We achieve sensitivities of 70%/83% at 3 FP/vol. and 84%/90% at 6 FP/vol. in mediastinum and abdomen respectively, which drastically improves over the previous state-of-the-art work. C1 [Roth, Holger R.; Lu, Le; Seff, Ari; Cherry, Kevin M.; Hoffman, Joanne; Wang, Shijun; Liu, Jiamin; Turkbey, Evrim; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Roth, HR (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM holger.roth@nih.gov NR 16 TC 32 Z9 32 U1 2 U2 8 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-10404-1; 978-3-319-10403-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8673 BP 520 EP 527 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC0GL UT WOS:000349019600065 ER PT S AU Seff, A Lu, L Cherry, KM Roth, HR Liu, JM Wang, SJ Hoffman, J Turkbey, EB Summers, RM AF Seff, Ari Lu, Le Cherry, Kevin M. Roth, Holger R. Liu, Jiamin Wang, Shijun Hoffman, Joanne Turkbey, Evrim B. Summers, Ronald M. BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI 2D View Aggregation for Lymph Node Detection Using a Shallow Hierarchy of Linear Classifiers SO Medical Image Computing and Computer-Assisted Intervention - MICCAI 2014, Pt I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol ID CT DATA; SEGMENTATION AB Enlarged lymph nodes (LNs) can provide important information for cancer diagnosis, staging, and measuring treatment reactions, making automated detection a highly sought goal. In this paper, we propose a new algorithm representation of decomposing the LN detection problem into a set of 2D object detection subtasks on sampled CT slices, largely alleviating the curse of dimensionality issue. Our 2D detection can be effectively formulated as linear classification on a single image feature type of Histogram of Oriented Gradients (HOG), covering a moderate field-of-view of 45 by 45 voxels. We exploit both max-pooling and sparse linear fusion schemes to aggregate these 2D detection scores for the final 3D LN detection. In this manner, detection is more tractable and does not need to perform perfectly at instance level (as weak hypotheses) since our aggregation process will robustly harness collective information for LN detection. Two datasets (90 patients with 389 mediastinal LNs and 86 patients with 595 abdominal LNs) are used for validation. Cross-validation demonstrates 78.0% sensitivity at 6 false positives/volume (FP/vol.) (86.1% at 10 FP/vol.) and 73.1% sensitivity at 6 FP/vol. (87.2% at 10 FP/vol.), for the mediastinal and abdominal datasets respectively. Our results compare favorably to previous state-of-the-art methods. C1 [Seff, Ari; Lu, Le; Cherry, Kevin M.; Roth, Holger R.; Liu, Jiamin; Wang, Shijun; Hoffman, Joanne; Turkbey, Evrim B.; Summers, Ronald M.] Natl Inst Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. RP Seff, A (reprint author), Natl Inst Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. NR 16 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-10404-1; 978-3-319-10403-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8673 BP 544 EP 552 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC0GL UT WOS:000349019600068 ER PT S AU Xu, ZY Bagci, U Seidel, J Thomasson, D Solomon, J Mollura, DJ AF Xu, Ziyue Bagci, Ulas Seidel, Jurgen Thomasson, David Solomon, Jeff Mollura, Daniel J. BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI Segmentation Based Denoising of PET Images: An Iterative Approach via Regional Means and Affinity Propagation SO Medical Image Computing and Computer-Assisted Intervention - MICCAI 2014, Pt I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol DE PET Denoising; PET Segmentation; Regional Means; Affinity Propagation; Generalized Anscombe Transformation AB Delineation and noise removal play a significant role in clinical quantification of PET images. Conventionally, these two tasks are considered independent, however, denoising can improve the performance of boundary delineation by enhancing SNR while preserving the structural continuity of local regions. On the other hand, we postulate that segmentation can help denoising process by constraining the smoothing criteria locally. Herein, we present a novel iterative approach for simultaneous PET image denoising and segmentation. The proposed algorithm uses generalized Anscombe transformation priori to non-local means based noise removal scheme and affinity propagation based delineation. For nonlocal means denoising, we propose a new regional means approach where we automatically and efficiently extract the appropriate subset of the image voxels by incorporating the class information from affinity propagation based segmentation. PET images after denoising are further utilized for refinement of the segmentation in an iterative manner. Qualitative and quantitative results demonstrate that the proposed framework successfully removes the noise from PET images while preserving the structures, and improves the segmentation accuracy. C1 [Xu, Ziyue; Bagci, Ulas; Seidel, Jurgen; Thomasson, David; Solomon, Jeff; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Bagci, U (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ulas.bagci@nih.gov OI Bagci, Ulas/0000-0001-7379-6829 NR 8 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-10404-1; 978-3-319-10403-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8673 BP 698 EP 705 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC0GL UT WOS:000349019600087 ER PT J AU Lee, JT Chou, CH Cho, NY Sung, YF Yang, FC Chen, CY Lai, YH Chiang, CI Chu, CM Lin, JC Hsu, YD Hong, JS Peng, GS Chuang, DM AF Lee, Jiunn-Tay Chou, Chung-Hsing Cho, Nai-Yu Sung, Yueh-Feng Yang, Fu-Chi Chen, Cheng-Yu Lai, Yu-Hua Chiang, Chun-I Chu, Chi-Ming Lin, Jiann-Chyun Hsu, Yaw-Don Hong, Jau-Shyong Peng, Giia-Sheun Chuang, De-Maw TI Post-insult valproate treatment potentially improved functional recovery in patients with acute middle cerebral artery infarction SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE Ischemic stroke; valproate; stroke outcome; neuroprotection ID ACUTE ISCHEMIC-STROKE; HISTONE DEACETYLASE INHIBITION; PROTECTS DOPAMINERGIC-NEURONS; MOOD STABILIZERS LITHIUM; POOLED ANALYSIS; BRAIN-DAMAGE; RAT MODEL; ACID; TRIALS; ROLES AB Animal stroke models suggest that valproate has multiple neuroprotective mechanisms against ischemic brain damage. This study investigated whether valproate improves functional recovery in patients with acute middle cerebral artery (MCA) infarction. This was an open-label controlled trial. Three to 24 hours after acute MCA infarction, patients were assigned to either the valproate group (n = 17) or the non-valproate group (n = 17). The valproate group received intravenous valproate (400 mg) at enrollment, and then every 12 hours for three days, followed by oral valproate (500 mg) every 12 hours for three months. Neurological function, laboratory data, and brain magnetic resonance imaging were examined at stroke onset, and at two-week and three-month follow-up. No significant differences were observed between the groups with regard to demographics or baseline characteristics. All patients were elderly, had a high pretreatment score on the NIH stroke scale (NIHSS), and slow stroke lesion growth with a final large infarct volume at two-week follow-up. At the three-month follow-up, functional outcome between pre- and post-treatment had improved significantly in the valproate group (NIHSS, p = 0.004; modified Rankin scale (mRS), p = 0.007; Barthel index (BI), p = 0.001). No such improvement was noted in the NIHSS or mRS for the non-valproate group, though mild improvement was seen on the BI (p = 0.022). This open-label trial is the first to demonstrate that valproate treatment markedly improves functional outcome in patients with acute MCA infarction. C1 [Lee, Jiunn-Tay; Chou, Chung-Hsing; Sung, Yueh-Feng; Yang, Fu-Chi; Lai, Yu-Hua; Chiang, Chun-I; Lin, Jiann-Chyun; Hsu, Yaw-Don; Peng, Giia-Sheun] Natl Def Med Ctr, Triserv Gen Hosp, Dept Neurol, Taipei 114, Taiwan. [Cho, Nai-Yu] Natl Def Med Ctr, Triserv Gen Hosp, Dept Radiol, Taipei 114, Taiwan. [Chen, Cheng-Yu] Taipei Med Univ, Taipei Med Univ Hosp, Dept Med Imaging, Taipei, Taiwan. [Lai, Yu-Hua] Triserv Gen Hosp, Dept Internal Med, Penghu Branch, Penghu, Taiwan. [Chiang, Chun-I] Hualien Armed Forces Gen Hosp, Dept Internal Med, Hualien, Taiwan. [Chu, Chi-Ming] Natl Def Med Ctr, Sch Publ Hlth, Dept Epidemiol, Taipei 114, Taiwan. [Hong, Jau-Shyong] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Peng, GS (reprint author), Natl Def Med Ctr, Triserv Gen Hosp, Dept Neurol, 325,Cheng Kung Rd Sect 2, Taipei 114, Taiwan. EM tsghpeng@gmail.com; chuang@mail.nih.gov FU Tri-Service General Hospital [TSGH-C98-11-S01-04, TS-GH-C99-11-S01-04, TSGH-C100-11-S01-3, TS-GH-C102-076, TSGH-C103-86]; Teh-Tzer study group for the Human Medical Research Foundation [A1001028-2]; Intramural Research Program, National Institutes of Health (IRP-NIH) FX The authors thank Chia Ping Tu, Hui Chen Lin, Pei-Min Hsiao, and Wei Tsai of the Tri-Service General Hospital for their professional care of the patients during the course of this study. Ioline Henter of the NIMH, NIH, USA provided excellent editorial assistance. This work was supported by grants from the Tri-Service General Hospital (TSGH-C98-11-S01-04; TS-GH-C99-11-S01-04; TSGH-C100-11-S01-3; TS-GH-C102-076; TSGH-C103-86), the Teh-Tzer study group for the Human Medical Research Foundation (A1001028-2), and the Intramural Research Program, National Institutes of Health (IRP-NIH). NR 34 TC 2 Z9 2 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2014 VL 6 IS 6 BP 820 EP 830 PG 11 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA AZ6AH UT WOS:000348299700018 PM 25628792 ER PT J AU Maeda, K Desai, DV Aoki, M Nakata, H Kodama, EN Mitsuya, H AF Maeda, Kenji Desai, Darshan V. Aoki, Manabu Nakata, Hirotomo Kodama, Eiichi N. Mitsuya, Hiroaki TI Delayed emergence of HIV-1 variants resistant to 4 '-ethynyl-2-fluoro-2 '-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-986001 SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITOR; AMINO-ACID DELETION; IN-VITRO; PROTEASE INHIBITORS; REPLICATION; INFECTION; POTENT; RECOMBINATION; CODON-67 AB Background: 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) contains an ethynyl moiety and the 3'-hydroxyl and exerts highly potent activity against various HIV type-1 (HIV-1) strains including multi-drug-resistant variants. Methods: Comparative selection passages against EFdA, lamivudine (3TC), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) or BMS-986001 (Ed4T) were conducted using a mixture of 11 highly multi-drug-resistant clinical HIV-1 isolates (HIV11MIX) as a starting virus population. Results: Before selection, HIV11MIX was sensitive to EFdA with a 50% inhibitory concentration (IC50) of 0.032 mM, less susceptible to TDF and Ed4T with IC(50)s of 0.57 and 2.6 mu M, respectively, and highly resistant to 3TC and FTC with IC(50)s>10 mu M. IC(50)s of TDF against HIV11MIX exposed to EFdA and TDF for 17 (HIV11MIXEFdA-P17) and 14 (HIV11MIXTDF-P14) passages were 8 and >10 mu M, respectively, while EFdA remained active against HIV11MIXEFdA-P17 and HIV11MIXTDF-P14 with IC(50)s of 0.15 and 0.1 mu M, respectively. Both selected variants were highly resistant against zidovudine, 3TC, Ed4T and FTC (IC50 values >10 mu M). Conclusions: The present data demonstrate that HIV11MIX developed resistance more rapidly against 3TC, FTC, TDF and Ed4T than against EFdA and that EFdA remained substantially active against TDF- and EFdA-selected variants. Thus, EFdA has a favourable resistance profile and represents a potentially promising new-generation nucleoside reverse transcriptase inhibitor. C1 [Maeda, Kenji; Desai, Darshan V.; Nakata, Hirotomo; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto, Japan. [Aoki, Manabu; Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto, Japan. [Aoki, Manabu; Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto, Japan. [Kodama, Eiichi N.] Tohoku Med Megabank Org, Tohoku Univ Hosp, Div Emerging Infect Dis, Sendai, Miyagi, Japan. RP Maeda, K (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. EM maedak@mail.nih.gov RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 FU Intramural NIH HHS NR 35 TC 4 Z9 4 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 IS 2 BP 179 EP 189 DI 10.3851/IMP2697 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CA0IK UT WOS:000348601000007 PM 24162098 ER PT J AU Havens, PL Hazra, R Stephensen, CB Kiser, JJ Flynn, PM Wilson, CM Rutledge, B Bethel, J Pan, CG Woodhouse, LR Van Loan, MD Liu, N Lujan-Zilbermann, J Baker, A Kapogiannis, BG Gordon, CM Mulligan, K AF Havens, Peter L. Hazra, Rohan Stephensen, Charles B. Kiser, Jennifer J. Flynn, Patricia M. Wilson, Craig M. Rutledge, Brandy Bethel, James Pan, Cynthia G. Woodhouse, Leslie R. Van Loan, Marta D. Liu, Nancy Lujan-Zilbermann, Jorge Baker, Alyne Kapogiannis, Bill G. Gordon, Catherine M. Mulligan, Kathleen CA Adolescent Med Trials Network HIV TI Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate SO ANTIVIRAL THERAPY LA English DT Article ID PARATHYROID-HORMONE; D DEFICIENCY; SECONDARY HYPERPARATHYROIDISM; THERAPY; CALCITRIOL; 1,25-DIHYDROXYVITAMIN-D; DIALYSIS; CALCIUM; BINDING; PROTEIN AB Background: Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D-binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biological activity, and is elevated in individuals with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youths treated with combination antiretroviral therapy (cART) containing or not containing TDF. Methods: A randomized controlled trial in HIV-positive youths aged 18-25 years enrolled participants based on cART treatment with TDF (TDF; n = 118) or without TDF (no-TDF; n = 85), and randomized within those groups to VITD (50,000 IU every 4 weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group. Results: At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was 7.7 pg/ml in the TDF/VITD group, compared with -1.7 (no-TDF/VITD, P = 0.010), -1.3 (TDF/PL, P = 0.006) and 1.1 (no-TDF/PL, P = 0.035). Conclusions: These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youths. Clinical trials number: NCT00490412. C1 [Havens, Peter L.; Pan, Cynthia G.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA. [Hazra, Rohan; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Stephensen, Charles B.; Woodhouse, Leslie R.; Van Loan, Marta D.] ARS, USDA, Western Human Nutr Res Ctr, Davis, CA USA. [Kiser, Jennifer J.] Univ Colorado, Dept Pharmaceut Sci, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Flynn, Patricia M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA. [Rutledge, Brandy; Bethel, James; Liu, Nancy] WESTAT Corp, Rockville, MD 20850 USA. [Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL USA. [Baker, Alyne] Tulane Univ, New Orleans, LA 70118 USA. [Gordon, Catherine M.] Hasbro Childrens Hosp, Providence, RI USA. [Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA. [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Havens, PL (reprint author), Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA. EM phavens@mcw.edu FU Cancer Research UK [RUL1-RR-024134]; NCRR NIH HHS [UL1 RR024134, M01 RR000188, M01 RR010710, M01 RR020359, M01-RR00188, M01-RR10710, M01RR020359, UL1 RR024131, UL1 RR025014, UL1-RR025014, UL1-RR02517]; NICHD NIH HHS [U01 HD 040474, U01 HD 040533, U01 HD040474, U01 HD040497, U01 HD040533] NR 20 TC 2 Z9 2 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 IS 6 BP 613 EP 618 DI 10.3851/IMP2755 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CA0JE UT WOS:000348603300010 PM 24535626 ER PT J AU Shahbazi, S Peer, CJ Figg, WD AF Shahbazi, Shandiz Peer, Cody J. Figg, William D. TI Prolonged low intensity EPOCH-rituximab has improved toxicity in Burkitt lymphoma compared with standard short, high intensity therapy SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE Burkitt lymphoma; EPOCH regimen; low-intensity therapy ID CELL LYMPHOMA; LEUKEMIA; ADULTS AB Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma that has a short doubling time, thus intense short-cycle chemotherapy has been thought to be essential. A recent NCI-sponsored clinical trial investigated DA-EPOCH-R given to 19 HIV-negative patients and a short course regimen (SC-EPOCH-RR) given to 11 HIV-positive patients in hopes of maintaining the efficacy of the regimen while decreasing the typical side effects from the intensive short-cycle chemotherapy. Low intensity EPOCH-R based therapy achieved excellent rates of efficacy despite a significant difference in the median cumulative dose between the DA-EPOCH-R and SC-EPOCH-RR cohorts. Furthermore, both cohorts experienced mainly grade 1 and grade 2 toxicities, with SC-EPOCH-RR cohort patients experiencing less adverse events than DA-EPOCH-R cohort patients. This recent clinical investigation suggests the most important therapeutic principle is not the intensity but rather the length of exposure time above an effective threshold concentration. Since short, intense bolus doses are the standard therapy for Burkitt lymphoma, these findings are clinically relevant and significant. C1 [Shahbazi, Shandiz; Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA. EM wf13e@nih.gov RI Figg Sr, William/M-2411-2016 NR 14 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2014 VL 15 IS 9 BP 1117 EP 1119 DI 10.4161/cbt.29504 PG 3 WC Oncology SC Oncology GA AZ6GY UT WOS:000348318700002 PM 24919059 ER PT J AU Srivastava, A Price, DK Figg, WD AF Srivastava, Anjali Price, Douglas K. Figg, William D. TI Prostate tumor development and androgen receptor function alterations in a new mouse model with ERG overexpression and PTEN inactivation SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE prostate; androgen receptor; ERG; PTEN; mouse model ID CANCER PROGRESSION; TMPRSS2-ERG; FUSION C1 [Srivastava, Anjali; Price, Douglas K.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 10 TC 0 Z9 0 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2014 VL 15 IS 10 BP 1293 EP 1295 DI 10.4161/cbt.29694 PG 3 WC Oncology SC Oncology GA AZ7EL UT WOS:000348381600001 PM 25007053 ER PT J AU Goey, AKL Figg, WD AF Goey, Andrew K. L. Figg, William D. TI Potential novel role of bevacizumab in glioblastoma and cervical cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE bevacizumab (Avastin); angiogenesis; VEGF-A; glioblastoma; cervical cancer ID CELL LUNG-CANCER; PHASE-III TRIAL; NEWLY-DIAGNOSED GLIOBLASTOMA; 1ST-LINE THERAPY; CHEMOTHERAPY; TEMOZOLOMIDE; GEMCITABINE; CARCINOMA; SURVIVAL; PLACEBO C1 [Goey, Andrew K. L.; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 16 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2014 VL 15 IS 10 BP 1296 EP 1298 DI 10.4161/cbt.29926 PG 3 WC Oncology SC Oncology GA AZ7EL UT WOS:000348381600002 PM 25046485 ER PT J AU Lochrin, SE Price, DK Figg, WD AF Lochrin, Sarah E. Price, Douglas K. Figg, William D. TI BET bromodomain inhibitors-A novel epigenetic approach in castration-resistant prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE androgen receptor; BET bromodomain inhibitor; castration-resistant prostate cancer; gene transcription ID ENZALUTAMIDE; CHEMOTHERAPY; PROTEINS AB The androgen receptor (AR) is central to the initiation and progression of prostate cancer, even after castration. There has been some success in therapies targeting AR signaling which have been shown to extend survival in men with castration-resistant prostate cancer (CRPC). However, durable responses to these therapies have been limited and there is a need to identify additional therapeutic targets within the AR-signaling network. Recently a group at University of Michigan Medical School outlined the potential for BET bromodomain protein inhibitors as a novel epigenetic approach to treatment of CRPC. In prostate cancer cell lines, BET bromodomain inhibitor, JQ1, was shown to induce apoptosis and down-regulate AR-regulated gene transcription. Bromodomain and the extra-terminal (BET) subfamily of human bromodomain proteins, with a focus on BRD4, were shown to play a major role in AR signaling and interact with AR via bromodomain (BD) 1/2. JQ1 inhibits this BRD4-AR bond, resulting in removal of RNA polymerase II from AR target genes, causing reduced AR gene transcription and subsequent diminished AR signaling. JQ1 lead to a significant reduction in tumor volume and weight in VCaP xenograft mice. C1 [Lochrin, Sarah E.; Price, Douglas K.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 11 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2014 VL 15 IS 12 BP 1583 EP 1585 DI 10.4161/15384047.2014.962297 PG 3 WC Oncology SC Oncology GA AZ7EP UT WOS:000348382100001 PM 25535892 ER PT J AU Carvalho, AF Miskowiak, KK Hyphantis, TN Kohler, CA Alves, GS Bortolato, B Sales, PMG Machado-Vieira, R Berk, M McIntyre, RS AF Carvalho, Andre F. Miskowiak, Kamilla K. Hyphantis, Thomas N. Koehler, Cristiano A. Alves, Gilberto S. Bortolato, Beatrice Sales, Paulo Marcelo G. Machado-Vieira, Rodrigo Berk, Michael McIntyre, Roger S. TI Cognitive Dysfunction in Depression - Pathophysiology and Novel Targets SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Brain-derived neurotrophic factor; cognition; cytokine; erythropoietin; inflammation; major depressive disorder; novel targets; oxidative stress; S-adenosyl-L-methionine ID RANDOMIZED CONTROLLED-TRIAL; TREATMENT-RESISTANT DEPRESSION; PLACEBO-CONTROLLED TRIAL; NITRIC-OXIDE SYNTHASE; ENDOPLASMIC-RETICULUM STRESS; TRAUMATIC BRAIN-INJURY; NF-KAPPA-B; MAJOR DEPRESSION; OXIDATIVE STRESS; DOUBLE-BLIND AB Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted. C1 [Carvalho, Andre F.; Alves, Gilberto S.; Sales, Paulo Marcelo G.] Univ Fed Ceara, Fac Med, Translat Psychiat Res Grp, BR-60430040 Fortaleza, Ceara, Brazil. [Miskowiak, Kamilla K.] Rigshosp, Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, DK-2100 Copenhagen, Denmark. [Hyphantis, Thomas N.] Univ Ioaninna, Sch Med, Dept Psychiat, Ioaninna, Greece. [Koehler, Cristiano A.] Fed Univ Rio Grande Norte UFRN, Brain Inst ICe, Memory Res Lab, Natal, RN, Brazil. [Bortolato, Beatrice] Univ Padua, Dept Neurosci, Padua, Italy. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Berk, Michael] Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. [Berk, Michael] Barwon Hlth, Geelong, Vic, Australia. [Berk, Michael] Univ Melbourne, Dept Psychiat, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Berk, Michael] Univ Melbourne, Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia. [McIntyre, Roger S.] Univ Toronto, Mood Disorders Psychopharmacol Unit, Toronto, ON, Canada. [McIntyre, Roger S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [McIntyre, Roger S.] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. RP Carvalho, AF (reprint author), Univ Fed Ceara, Fac Med, Dept Clin Med, Rua Prof Costa Mendes,1608,4o Andar, BR-60430040 Fortaleza, Ceara, Brazil. EM andrefc7@terra.com.br RI Kohler, Cristiano/A-6381-2013; MACHADO-VIEIRA, RODRIGO/D-8293-2012; OI Kohler, Cristiano/0000-0003-0503-5264; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Berk, Michael/0000-0002-5554-6946 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; Level II); CAPES FX AFC is supported by a research fellowship award from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; Level II). CAK is supported by a postdoctoral fellowship from CAPES. NR 257 TC 21 Z9 22 U1 14 U2 33 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 10 BP 1819 EP 1835 PG 17 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CA0GG UT WOS:000348594400017 PM 25470397 ER PT J AU White, AB Mirjahangir, JF Horvath, H Anglemyer, A Read, JS AF White, Angela B. Mirjahangir, Joy F. Horvath, Hacsi Anglemyer, Andrew Read, Jennifer S. TI Antiretroviral interventions for preventing breast milk transmission of HIV SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID TO-CHILD TRANSMISSION; DOSE NEVIRAPINE PROPHYLAXIS; RANDOMIZED CLINICAL-TRIAL; IMMUNODEFICIENCY-VIRUS TYPE-1; SUB-SAHARAN AFRICA; DAR-ES-SALAAM; VERTICAL TRANSMISSION; HIV-1-INFECTED WOMEN; INFECTED WOMEN; SOUTH-AFRICA AB Background An estimated 260,000 children under the age of 15 years acquired HIV infection in 2012. As much as 42% of mother-to-child transmission is related to breastfeeding. Antiretroviral prophylaxis for mothers or infants has the potential to prevent mother-to-child transmission of HIV through breast milk. Objectives To determine which antiretroviral prophylactic regimens are efficacious and safe for reducing mother-to-child transmission of HIV through breastfeeding and thereby avert child morbidity and mortality. Search methods Using Cochrane Collaboration search methods in conjunction with appropriate search terms, we identified relevant studies from January 1, 1994 to January 14, 2014 by searching databases including Cochrane CENTRAL, EMBASE and PubMed, LILACS, and Web of Science/Web of Social Science. Selection criteria Randomized controlled trials in which HIV-infected mothers breastfed their infants, and in which the mothers used antiretroviral prophylaxis while breastfeeding their children or their children received antiretroviral prophylaxis for at least four weeks while breastfeeding, were included. Data collection and analysis Abstracts of all trials identified were examined independently by two authors. We identified 15,922 references and examined 81 in detail. Data were abstracted independently using a standardized form. Main results Seven RCTs were included in the review. One trial compared triple antiretroviral prophylaxis during pregnancy and breastfeeding with short antiretroviral prophylaxis to given to the mother to prevent mother-to-child transmission of HIV. At 12 months, the risks of HIV transmission, and of HIV transmission or death, were lower, but there was no difference in infant mortality alone in the triple arm versus the short arm. Using the GRADE methodology, evidence quality for outcomes in this trial was generally low to moderate. One trial compared six months of breastfeeding using zidovudine, lamivudine, and lopinavir/ritonavir versus zidovudine, lamivudine, and abacavir from 26-34 weeks gestation. At six months, there was no difference in risk of infant HIV infection, infant death, or infant HIV infection or death between the two groups. Evidence quality for outcomes in this trial was generally very low to low. One trial of single dose nevirapine versus six weeks of infant zidovudine found the risk of HIV infection at 12 weeks to be greater in the zidovudine arm than in the single dose nevirapine arm. Evidence quality for outcomes in this trial was generally very low. One multi-country trial compared single dose nevirapine and six weeks of infant nevirapine. After 12 months, infants in the extended nevirapine group had a lower risk of infant mortality compared with the control. There was no difference in the risk of HIV infection or death or in HIV transmission alone in the extended nevirapine group compared with the control. Evidence quality for outcomes in this trial was generally low to moderate. One trial compared single dose nevirapine plus one week zidovudine; the control regimen plus nevirapine up to 14 weeks; or the control regimen with dual prophylaxis up to 14 weeks. At 24 months, the extended nevirapine regimen group had a lower risk of HIV transmission and of HIV transmission or death vs. the control. There was no difference in infant mortality alone. Compared with controls, the dual prophylaxis group had a lower risk of HIV transmission and of HIV transmission or death, but no difference in infant mortality alone. There was no difference in these outcomes between the two intervention arms. Evidence quality for outcomes in this trial was generally moderate to high. One trial compared sixweeks of nevirapine with six months of nevirapine. Among infants of mothers not using highly active antiretroviral therapy, there was no difference in risk of HIV infection among the six month nevirapine group versus the six week nevirapine group. Evidence quality for outcomes in this trial was generally low to moderate. One trial compared a maternal triple-drug antiretroviral regimen, infant nevirapine, or neither intervention. Infants in the maternal prophylaxis arm were at lower risk for HIV, and HIV infection or death when compared with the control group. There was no difference in the risk of infant mortality alone. Infants with extended prophylaxis had a lower risk of HIV infection and of HIV infection or death versus the control group infants. There was no difference in the risk of infant mortality alone in the extended infant nevirapine group versus the control. There was no difference in HIV infection, infant mortality, and HIV infection or death between the maternal and extended infant prophylaxis groups. Evidence quality for outcomes in this trial was generally low to moderate. Authors' conclusions Antiretroviral prophylaxis, whether used by the HIV-infected mother or the HIV-exposed infant while breastfeeding, is efficacious in preventing mother-to-child transmission of HIV. Further research is needed regarding maternal resistance and response to subsequent antiretroviral therapy after maternal prophylaxis. An ongoing trial (IMPAACT 1077BF) compares the efficacy and safety of maternal triple antiretroviral prophylaxis versus daily infant nevirapine for prevention of mother-to-child transmission through breastfeeding. C1 [White, Angela B.; Mirjahangir, Joy F.; Horvath, Hacsi; Anglemyer, Andrew; Read, Jennifer S.] Univ Calif San Francisco, San Francisco, CA 94105 USA. [Read, Jennifer S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Mirjahangir, JF (reprint author), Univ Calif San Francisco, 50 Beale St,12th Floor, San Francisco, CA 94105 USA. EM jmirjahangir@psg.ucsf.edu FU Global Health Sciences, University of California, San Francisco, USA; World Health Organization, Switzerland FX Internal sources; Global Health Sciences, University of California, San Francisco, USA.; External sources; World Health Organization, Switzerland.; The World Health Organization (WHO) commissioned the first iteration of this review in 2009 to inform WHO's 2010 PMTCT guidelines. That version of the review was never published. While we incorporate our work from the earlier review, we conducted the current updated and expanded review without external funding from any source. NR 91 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 10 AR CD011323 DI 10.1002/14651858.CD011323 PG 136 WC Medicine, General & Internal SC General & Internal Medicine GA AY5YW UT WOS:000347646000082 PM 25280769 ER PT J AU Anderson, BL Gigerenzer, G Parker, S Schulkin, J AF Anderson, Britta L. Gigerenzer, Gerd Parker, Scott Schulkin, Jay TI Statistical Literacy in Obstetricians and Gynecologists SO JOURNAL FOR HEALTHCARE QUALITY LA English DT Article DE academic; evidence-based practice/guidelines; practice setting/focus; research; research-evaluation; topics ID DECISION-MAKING; NUMERACY SCALE; COMMUNICATION AB The Obstetrician-Gynecologist Statistical Literacy Questionnaire (OGSLQ) was designed to examine physicians' understanding of various number tasks that are relevant to obstetrician-gynecologists (ob-gyns) practice. Forty-seven percent of the nationally representative, practicing ob-gyns responded. Physicians did poorly on the questions about numerical facts (e.g., number of women living with HIV/AIDS), better on questions about statistical concepts (e.g., incidence, prevalence), and best on questions about numerical relationships (e.g., convert frequency to percentage) with 0%, 7%, 36%, answering all correctly, respectively. Only 19% correctly estimated the number of U.S. women with cancer. Sixty-six percent were able to use sensitivity and specificity to choose a test option. Around 90% could translate between frequency and probability formats. Forty-nine percent of respondents were able to calculate the positive predictive value of a mammography screening test. Physicians lack some understanding of statistical literacy. It is important that we monitor physicians' statistical literacy and provide training to students and physicians. C1 [Anderson, Britta L.; Schulkin, Jay] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. [Gigerenzer, Gerd] Max Planck Inst Human Dev, Berlin, Germany. [Gigerenzer, Gerd] Harding Ctr Risk Literacy, Berlin, Germany. [Parker, Scott] Amer Univ, Washington, DC 20016 USA. [Parker, Scott] Amer Univ, Affiliated Fac, Dept Math & Stat, Washington, DC 20016 USA. [Schulkin, Jay] Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. [Schulkin, Jay] NIMH, Behav Endocrinol Branch, Washington, DC USA. RP Anderson, BL (reprint author), Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. EM anderson.britta.l@gmail.com FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal, and Child Health Research Program [UA6MC19010] FX This study is funded by grant, UA6MC19010, through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal, and Child Health Research Program. NR 21 TC 8 Z9 8 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1062-2551 EI 1945-1474 J9 J HEALTHC QUAL JI J. Healthc. Qual. PD JAN-FEB PY 2014 VL 36 IS 1 BP 5 EP 17 DI 10.1111/j.1945-1474.2011.00194.x PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AZ8FB UT WOS:000348449200001 PM 22292459 ER PT J AU Ezzo, J Richardson, MA Vickers, A Allen, C Dibble, S Issell, BF Lao, LX Pearl, M Ramirez, G Roscoe, JA Shen, J Shivnan, JC Streitberger, K Treish, I Zhang, G Manheimer, E AF Ezzo, Jeanette Richardson, Mary Ann Vickers, Andrew Allen, Claire Dibble, Suzanne Issell, Brian F. Lao, Lixing Pearl, Michael Ramirez, Gilbert Roscoe, Joseph A. Shen, Joannie Shivnan, Jane C. Streitberger, Konrad Treish, Imad Zhang, Grant Manheimer, Eric TI Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting (Withdrawn Paper. 2014. CD002285) SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Correction C1 [Ezzo, Jeanette] James P Swyers Enterprises, Baltimore, MD 21209 USA. [Richardson, Mary Ann] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, Integrat Med Serv, New York, NY 10021 USA. [Allen, Claire] Cochrane Collaborat Evidence Aid, Chief Execut Officers Off, Oxford, England. [Dibble, Suzanne] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA USA. [Issell, Brian F.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Lao, Lixing] Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China. [Pearl, Michael] Long Isl Gynecol Oncologists PC, Smithtown, NY USA. [Ramirez, Gilbert] W Virginia Univ, Sch Publ Hlth, Morgantown, WV 26506 USA. [Roscoe, Joseph A.] Univ Rochester, Ctr Canc, Behav Med Unit, Rochester, NY USA. [Shen, Joannie] Ctr Dis Control & Prevent, Atlanta, GA USA. [Shivnan, Jane C.] Inst Johns Hopkins Hosp, Baltimore, MD USA. [Streitberger, Konrad] Heidelberg Univ, Dept Anesthesiol, Heidelberg, Germany. [Treish, Imad] King Hussein Canc Ctr, Dept Pharm, Amman, Jordan. [Zhang, Grant] Univ Maryland, Sch Med, Ctr Integrat Med, Ellicott City, MD USA. [Manheimer, Eric] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. RP Ezzo, J (reprint author), James P Swyers Enterprises, 1905 West Rogers Ave, Baltimore, MD 21209 USA. EM jeanetteezzo@gmail.com FU Danish Cancer Society, Denmark; ViFab, Denmark; National Cancer Institute / National Center for Complementary and Alternative Medicine, USA [5 U24 CA66826-03] FX External sources; Danish Cancer Society, Denmark.; ViFab, Denmark.; National Cancer Institute / National Center for Complementary and Alternative Medicine 5 U24 CA66826-03, USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 11 AR CD002285 DI 10.1002/14651858.CD002285.pub3 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AY5YY UT WOS:000347646200007 PM 25412832 ER PT S AU Wong, KCL Summers, RM Kebebew, E Yao, JH AF Wong, Ken C. L. Summers, Ronald M. Kebebew, Electron Yao, Jianhua BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI Tumor Growth Prediction with Hyperelastic Biomechanical Model, Physiological Data Fusion, and Nonlinear Optimization SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2014, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol ID DIFFUSION AB Tumor growth prediction is usually achieved by physiological modeling and model personalization from clinical measurements. Although image-based frameworks have been proposed with promising results, different issues such as infinitesimal strain assumption, complicated optimization procedures, and lack of functional information, may limit the prediction performance. Therefore, we propose a framework which comprises a hyperelastic biomechanical model for better physiological plausibility, gradient-free nonlinear optimization for more flexible choices of models and objective functions, and physiological data fusion of structural and functional images for better subject-specificity. Experiments were performed on synthetic and clinical data to verify parameter estimation capability and prediction performance of the framework. Comparisons of using different biomechanical models and objective functions were also performed. From the experimental results on eight patient data sets, the recall, precision, and relative volume difference (RVD) between predicted and measured tumor volumes are 84.85+/-6.15%, 87.08+/-7.83%, and 13.81+/-6.64% respectively. C1 [Wong, Ken C. L.; Summers, Ronald M.; Yao, Jianhua] NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Kebebew, Electron] NIH, Natl Canc Inst, Endocrine Oncol Branch, Bethesda, MD 20892 USA. RP Wong, KCL (reprint author), NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-10470-6; 978-3-319-10469-0 J9 LECT NOTES COMPUT SC PY 2014 VL 8674 BP 25 EP 32 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BB8WS UT WOS:000347686400004 ER PT J AU Souza, TP Lorenco-Lima, L Ganini, D Vardaris, CV Polotow, TG Barros, MP AF Souza-Junior, T. P. Lorenco-Lima, L. Ganini, D. Vardaris, C. V. Polotow, T. G. Barros, M. P. TI DELAYED URIC ACID ACCUMULATION IN PLASMA PROVIDES ADDITIONAL ANTIOXIDANT PROTECTION AGAINST IRON-TRIGGERED OXIDATIVE STRESS AFTER A WINGATE TEST SO BIOLOGY OF SPORT LA English DT Article DE anaerobic metabolism; exercise; haemoglobin; lipid peroxidation; xanthine oxidase ID FREE-RADICALS; EXERCISE; DAMAGE; BIOMARKERS AB Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5-60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis. C1 [Souza-Junior, T. P.] Fed Univ Parana UFPR, Dept Phys Educ, Curitiba, Parana, Brazil. [Lorenco-Lima, L.; Vardaris, C. V.; Polotow, T. G.; Barros, M. P.] Cruzeiro do Sul Univ, Inst Phys Act & Sports Sci ICAFE, Postgrad Program Human Movement Sci, Sao Paulo, Brazil. [Ganini, D.] NIEHS, Free Rad Metab Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Barros, MP (reprint author), Univ Cruzeiro Sul, Inst Phys Act & Sports Sci ICAFE, R Galvao Bueno,868,13 Andar,Bloco B, BR-01506000 Sao Paulo, Brazil. EM marcelo.barros@cruzeirodosul.edu.br RI Barros, Marcelo/K-1410-2013 OI Barros, Marcelo/0000-0003-3565-8331 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2002/09405-9]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade, Nivel 2, Brazil) [CNPq 307474/2012-7]; Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES) FX The authors are indebted to the Brazilian funding agencies Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP 2002/09405-9), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade, Nivel 2, CNPq 307474/2012-7, Brazil), and Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES). Dr. Tacito Pessoa de Souza-Junior is also indebted to Dr. Antonio Carlos da Silva, Federal University of Sao Paulo, for experimental/equipment support. Dr. Marcelo Paes de Barros is indebted to Dr. Paulo Freitas, ICAFE/Universidade Cruzeiro do Sul for substantial support on statistical analysis, and to Prot Rui Curi (ICB/USP) and Prof. Etelvino J.H. Bechara (UNIFESP-Diadema) for the scientific review of our work. NR 19 TC 4 Z9 5 U1 0 U2 2 PU INST SPORT PI WARSAW 45 PA TRYLOGII 2, POB 30,, 01-892 WARSAW 45, POLAND SN 0860-021X J9 BIOL SPORT JI Biol. Sport PY 2014 VL 31 IS 4 BP 271 EP 276 DI 10.5604/20831862.1120934 PG 6 WC Sport Sciences SC Sport Sciences GA AY2RK UT WOS:000347436700004 PM 25435669 ER PT J AU Andrade, D Kim, M Blanco, LP Karumanchi, SA Koo, GC Redecha, P Kirou, K Alvarez, AM Mulla, MJ Crow, MK Abrahams, VM Kaplan, MJ Salmon, JE AF Andrade, Danieli Kim, Mimi Blanco, Luz P. Karumanchi, S. Ananth Koo, Gloria C. Redecha, Patricia Kirou, Kyriakos Alvarez, Angela M. Mulla, Melissa J. Crow, Mary K. Abrahams, Vikki M. Kaplan, Mariana J. Salmon, Jane E. TI Interferon-alpha and angiogenic dysregulation in pregnant lupus patients destined for preeclampsia SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT Conference on Lupus - New Targets, New Approaches CY SEP 18-20, 2014 CL Quebec, CANADA C1 [Andrade, Danieli; Koo, Gloria C.; Redecha, Patricia; Kirou, Kyriakos; Crow, Mary K.; Salmon, Jane E.] Hosp Special Surg, New York, NY 10021 USA. [Andrade, Danieli; Koo, Gloria C.; Redecha, Patricia; Kirou, Kyriakos; Crow, Mary K.; Salmon, Jane E.] Weill Cornell Med Coll, New York, NY USA. [Kim, Mimi] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Blanco, Luz P.; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Karumanchi, S. Ananth] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Alvarez, Angela M.] Univ Antioquia, Sch Med, Medellin, Colombia. [Alvarez, Angela M.; Mulla, Melissa J.; Abrahams, Vikki M.] Yale Univ, Sch Med, New Haven, CT USA. EM salmonj@hss.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 SU 1 MA A28 PG 1 WC Rheumatology SC Rheumatology GA AX9IK UT WOS:000347216600029 ER PT J AU Kuranov, AB Kotter, I Henes, JC Abisheva, ST Steiert, I Riewerts, F Momynaliev, KT Muller, CA AF Kuranov, Alexandr Borisovich Koetter, Ina Henes, Joerg Christoph Abisheva, Saule Tleubaevna Steiert, Ingeborg Riewerts, Florian Momynaliev, Kuvat Temirgalievich Mueller, Claudia Anna TI Behcet's disease in HLA-B*51 negative Germans and Turks shows association with HLA-Bw4-80I SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID HLA-B; INHIBITORY RECEPTOR; GENES; RECOGNITION; KIR3DL1; CELLS; SUSCEPTIBILITY; EXPRESSION; MOLECULES; GENETICS AB Introduction: Behcet's disease (BD) as systemic vasculitis of unknown etiology is associated with HLA-B*51 in European and Asian populations. HLA-A*26 was claimed as an additional BD susceptibility marker in Japanese and Greek patients. This study was performed to test for HLA associations in HLA-B*51 negative German and Turkish BD populations. Methods: In total, 65 German and 46 Turkish patients lacking HLA-B*51 were analyzed in comparison to healthy HLA-B*51 negative Germans (n = 1500) and Turks (n = 130). HLA-A/B genotypes were determined by SSOP. P-values with correction for multiple testing (p(c)), X-2-test and odds ratio (OR) were used for statistical evaluation. Results: HLA-A*26 was significantly more frequent in HLA-B*51(-) German patients [p(c) = 0.0076, OR = 3.23, 95% CI 1.63 to 6.39] than in respective controls. HLA-A*26 was also elevated in a smaller group of Turkish patients versus the controls. Significant association of HLA-Bw4 with isoleucine at amino-acid position 80 (HLA-Bw4-80I) was found in the HLA-B*51(-) German cohort of BD patients [p(c) = 0.0042, OR = 2.35, 95% CI 1.41 to 3.93) and in the Turkish patients in comparison to the respective controls [p = 0.025, OR = 2.17, 95% CI 1.09 to 4.31]. On the contrary, HLA-Bw4-80 T was reduced in both HLA-B*51(-) BD patient cohorts. Conclusions: The study shows a significant association of HLA-Bw4-80I present on HLA-B*51 as well as on other B-locus molecules with BD. This indicates that distinctive Bw4 epitopes on HLA-B locus molecules could play a role in BD pathogenesis. The study also indicates an association with HLA-A*26 in German and Turkish BD patients as a genetic risk factor independent of HLA-B*51. C1 [Kuranov, Alexandr Borisovich; Steiert, Ingeborg; Mueller, Claudia Anna] Univ Tubingen, Dept Internal Med 2, Sect Transplantat Immunol & Immunohematol, Tubingen, Germany. [Koetter, Ina] Interdisciplinary Ctr Rheumatol Stuttgart ZIRS, Stuttgart, Germany. [Henes, Joerg Christoph; Riewerts, Florian] Univ Tubingen, Ctr Interdisciplinary Clin Immunol, Rheumatol & Autoinflammatory Dis INDIRA, Tubingen, Germany. [Henes, Joerg Christoph; Steiert, Ingeborg] Univ Tubingen, Dept Internal Med 2, Tubingen, Germany. [Abisheva, Saule Tleubaevna] Sci Res Inst Traumatol & Orthoped, Astana, Kazakhstan. [Momynaliev, Kuvat Temirgalievich] Natl Ctr Biotechnol, Astana, Kazakhstan. RP Kuranov, AB (reprint author), Univ Tubingen, Dept Internal Med 2, Sect Transplantat Immunol & Immunohematol, Waldhoernle Str 22, Tubingen, Germany. EM iskander.kuranov@gmail.com FU German Academic Exchange Service (DAAD); Deutsche Forschungsgemeinschaft; Tubingen University FX We would like to thank all donors enrolled in the current study. We acknowledge support by the German Academic Exchange Service (DAAD) for ABK. We also thank C Bauer and A Petz (Section for Transplantation Immunology and Immunohematology, University of Tubingen) for technical assistance in HLA-typing. We acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tubingen University. This work was supported in part by an intramural funding. NR 34 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 3 AR R116 DI 10.1186/ar4569 PG 6 WC Rheumatology SC Rheumatology GA AX7EC UT WOS:000347078700011 PM 24887019 ER PT J AU Roopenian, DC Adkins, EB Park, G Morse, HC Carter, GW AF Roopenian, Derry C. Adkins, Elisabeth B. Park, Giljun Morse, Herbert C., III Carter, Gregory W. TI Modeling the stochastic behavior of lupus SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT Conference on Lupus - New Targets, New Approaches CY SEP 18-20, 2014 CL Quebec, CANADA C1 [Roopenian, Derry C.; Adkins, Elisabeth B.; Park, Giljun; Carter, Gregory W.] Jackson Lab, Bar Harbor, ME 04609 USA. [Adkins, Elisabeth B.] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Morse, Herbert C., III] NIAID, Rockville, MD USA. EM derry.roopenian@jax.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 SU 1 MA A6 PG 2 WC Rheumatology SC Rheumatology GA AX9IK UT WOS:000347216600007 ER PT J AU Rose, S Dave, J Millo, C Naik, HB Siegel, EL Mehta, NN AF Rose, Shawn Dave, Jenny Millo, Corina Naik, Haley B. Siegel, Evan L. Mehta, Nehal N. TI Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID RADIOLOGICAL GRADING CRITERIA; RISK-FACTORS; CLASSIFICATION CRITERIA; CARDIOVASCULAR-DISEASE; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; FDG-PET/CT; MORTALITY; DIAGNOSIS; FLUORODEOXYGLUCOSE AB Introduction: Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD. Methods: Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUVmax), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with beta-coefficients (beta) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors. Results: Vascular inflammation (measured as SUVmax) was greater (P < 0.001) in patients with sacroiliitis (mean +/- SD = 7.33 +/- 2.09) defined by CT compared to those without sacroiliitis (6.39 +/- 1.49, P = 0.038). There were associations between PsA and aortic inflammation (beta = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (beta = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (chi(2) = 124.6, P < 0.001). Conclusions: Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings. C1 [Rose, Shawn; Dave, Jenny; Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometabol Dis, NIH, Bethesda, MD 20892 USA. [Rose, Shawn] NIAMSD, NIAMS, NIH, Bethesda, MD 20892 USA. [Millo, Corina] NIH, Nucl Med Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. [Naik, Haley B.] NCI, NIH, Bethesda, MD 20892 USA. [Siegel, Evan L.] Arthrit & Rheumatism Associate, Rockville, MD 20850 USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometabol Dis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov FU National Institutes of Health Center; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) FX The authors would like to thank Daniel Shin for helpful discussions regarding statistical methodologies described in the manuscript and Robert Colbert for critical appraisal of the manuscript. This work was supported by intramural funding from the National Institutes of Health Center, the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). NR 53 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 4 AR R161 DI 10.1186/ar4676 PG 9 WC Rheumatology SC Rheumatology GA AX7EJ UT WOS:000347079500026 PM 25078679 ER PT J AU Singh, N Traisak, P Martin, KA Kaplan, MJ Cohen, PL Denny, MF AF Singh, Namrata Traisak, Pamela Martin, Kayla A. Kaplan, Mariana J. Cohen, Philip L. Denny, Michael F. TI Genomic alterations in abnormal neutrophils isolated from adult patients with systemic lupus erythematosus SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; REGULATORY FACTOR-I; COPY NUMBER ALTERATIONS; DOUBLE-STRAND BREAK; DNA-REPAIR GENES; MYELODYSPLASTIC SYNDROMES; MICROSATELLITE INSTABILITY; MYELOPROLIFERATIVE DISORDERS; HEMATOLOGICAL MALIGNANCIES AB Introduction: Patients with systemic lupus erythematosus (SLE) have an abnormal population of neutrophils, called low-density granulocytes (LDGs), that express the surface markers of mature neutrophils, yet their nuclear morphology resembles an immature cell. Because a similar discrepancy in maturation status is observed in myelodysplasias, and disruption of neutrophil development is frequently associated with genomic alterations, genomic DNA isolated from autologous pairs of LDGs and normal-density neutrophils was compared for genomic changes. Methods: Alterations in copy number and losses of heterozygosity (LOH) were detected by cytogenetic microarray analysis. Microsatellite instability (MSI) was detected by capillary gel electrophoresis of fluorescently labeled PCR products. Results: Control neutrophils and normal-density SLE neutrophils had similar levels of copy number variations, while the autologous SLE LDGs had an over twofold greater number of copy number alterations per genome. The additional copy number alterations found in LDGs were prevalent in six of the thirteen SLE patients, and occurred preferentially on chromosome 19, 17, 8, and X. These same SLE patients also displayed an increase in LOH. Several SLE patients had a common LOH on chromosome 5q that includes several cytokine genes and a DNA repair enzyme. In addition, three SLE patients displayed MSI. Two patients displayed MSI in greater than one marker, and one patient had MSI and increased copy number alterations. No correlations between genomic instability and immunosuppressive drugs, disease activity or disease manifestations were apparent. Conclusions: The increased level of copy number alterations and LOH in the LDG samples relative to autologous normal-density SLE neutrophils suggests somatic alterations that are consistent with DNA strand break repair, while MSI suggests a replication error-prone status. Thus, the LDGs isolated have elevated levels of somatic alterations that are consistent with genetic damage or genomic instability. This suggests that the LDGs in adult SLE patients are derived from cell progenitors that are distinct from the autologous normal-density neutrophils, and may reflect a role for genomic instability in the disease. C1 [Singh, Namrata; Traisak, Pamela; Cohen, Philip L.; Denny, Michael F.] Temple Univ, Rheumatol Sect, Philadelphia, PA 19140 USA. [Martin, Kayla A.; Cohen, Philip L.; Denny, Michael F.] Temple Univ, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. [Kaplan, Mariana J.] NIAMS NIH, Syst Autoimmun Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Cohen, Philip L.; Denny, Michael F.] Temple Univ, Temple Autoimmun Ctr, Philadelphia, PA 19140 USA. RP Denny, MF (reprint author), Temple Univ, Rheumatol Sect, 3322 North Broad St, Philadelphia, PA 19140 USA. EM mfdenny@temple.edu FU Lupus Research Institute; Alliance for Lupus Research; NIAMS [R01 DE017590, R03 AR061026]; Department of Medicine at Temple University; [P30 C4006927] FX The authors are grateful for excellent technical support provided by Dr Jianming Pei and the Cytogenetic Microarray Core facility at Fox Chase Cancer Center (supported by P30 C4006927). We also appreciate the many suggestions and helpful comments of Dr. Brendan Hillard. This research was supported by a grant from the Lupus Research Institute to MJK and a Target Identification in Lupus grant from the Alliance for Lupus Research to MFD. This was study was performed while MJK was employed at the University of Michigan. The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government MFD was also supported in part by a research supplement to R01 DE017590 (PLC), NIAMS New Investigator, Award R03 AR061026, and a Faculty Research Development Award from the Department of Medicine at Temple University. Research conducted by NS and PT in partial fulfillment of the requirements for fellows participation in the Rheumatology Research Training Program at Temple University. NR 100 TC 6 Z9 7 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 4 AR R165 DI 10.1186/ar4681 PG 13 WC Rheumatology SC Rheumatology GA AX7EJ UT WOS:000347079500030 PM 25107306 ER PT J AU Tektonidou, M Dasgupta, A Ward, M AF Tektonidou, Maria Dasgupta, Abhijit Ward, Michael TI Methodological quality of studies of end-stage renal disease risks in lupus nephritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT Conference on Lupus - New Targets, New Approaches CY SEP 18-20, 2014 CL Quebec, CANADA C1 [Tektonidou, Maria] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Dasgupta, Abhijit; Ward, Michael] NIAMSD, NIH, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 SU 1 MA A47 PG 1 WC Rheumatology SC Rheumatology GA AX9IK UT WOS:000347216600048 ER PT J AU Castaneto, MS Desrosiers, NA Ellefsen, K Anizan, S Martin, TM Klette, KL Huestis, MA AF Castaneto, Marisol S. Desrosiers, Nathalie A. Ellefsen, Kayla Anizan, Sebastien Martin, Thomas M. Klette, Kevin L. Huestis, Marilyn A. TI Method validation of the biochip array technology for synthetic cannabinoids detection in urine SO BIOANALYSIS LA English DT Article ID TANDEM MASS-SPECTROMETRY; LC-MS/MS; ILLEGAL PRODUCTS; DESIGNER DRUGS; WHOLE-BLOOD; ORAL FLUID; METABOLITES; QUANTIFICATION; JWH-018; IDENTIFICATION AB Background: Synthetic cannabinoids (SC) are widely-abused cannabimimetic drugs that do not screen positive in traditional cannabinoids immunoassays, making detection difficult. Methods & results: The first commercially-available immunoassay for urinary SC was validated. Limits of detection (5-20 mu g/L), imprecision (< 13.1% intra-, < 37.7% inter-assay), and cross-reactivity profiles of 22 SC and 37 metabolites were obtained. A large negative bias (-80.8 to -28.0%) was observed. Sensitivity (98.3%), specificity (48.1%) and efficiency (53.9%) were determined from screening 20,017 urine specimens and confirming 1432 presumptive positive and 1069 selected negative specimens by LC-MS/MS. Cutoff optimization improved performance to 87.6% sensitivity, 85.2% specificity, and 85.4% efficiency. Conclusion: This high-throughput urine SC assay has good sensitivity and improved specificity and efficiency at modified cutoff concentrations. C1 [Castaneto, Marisol S.; Desrosiers, Nathalie A.; Ellefsen, Kayla; Anizan, Sebastien; Huestis, Marilyn A.] NIDA, NIH, Baltimore, MD 21224 USA. [Castaneto, Marisol S.; Desrosiers, Nathalie A.; Ellefsen, Kayla] Univ Maryland, Program Toxicol, Baltimore, MD 21201 USA. [Martin, Thomas M.; Klette, Kevin L.] Off Secretary Def Operat Readiness & Safety, Washington, DC USA. RP Huestis, MA (reprint author), NIDA, NIH, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Department of Defense Counter Narcotics Program; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, NIH FX An Interagency Agreement between Department of Defense Counter Narcotics Program and the Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, NIH helped fund this research. Randox supplied some reagents and provided the Evidence (R) Analyzer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 33 TC 2 Z9 2 U1 2 U2 5 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 21 SI SI BP 2919 EP 2930 DI 10.4155/BIO.14.150 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AX1HZ UT WOS:000346699600012 PM 25486237 ER PT J AU Esen, T Turkbey, B Patel, A Futterer, J AF Esen, Tarik Turkbey, Baris Patel, Anup Futterer, Jurgen TI Multiparametric MRI in Prostate Cancer SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material ID RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; BIOPSY C1 [Esen, Tarik] Koc Univ, Sch Med, Dept Urol, TR-34450 Istanbul, Turkey. [Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Patel, Anup] Royal London Hosp, Barts Hlth NHS Trust, London E1 1BB, England. [Futterer, Jurgen] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6500 HB Nijmegen, Netherlands. RP Esen, T (reprint author), Koc Univ, Sch Med, Dept Urol, TR-34450 Istanbul, Turkey. EM tarikesen@doruk.net.tr NR 15 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 296810 DI 10.1155/2014/296810 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AY0WX UT WOS:000347316000001 ER PT J AU Johnson, LM Choyke, PL Figg, WD Turkbey, B AF Johnson, Linda M. Choyke, Peter L. Figg, William D. Turkbey, Baris TI The Role of MRI in Prostate Cancer Active Surveillance SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID DIFFUSION-WEIGHTED MRI; CONTRAST-ENHANCED MRI; RADICAL PROSTATECTOMY; ENDORECTAL COIL; NATURAL-HISTORY; BIOPSY STRATEGY; TARGETED BIOPSY; 3 T; RESONANCE; ANTIGEN AB Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance. C1 [Johnson, Linda M.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20852 USA. [Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, Bethesda, MD 20852 USA. [Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20852 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20852 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 51 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 203906 DI 10.1155/2014/203906 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AY0UI UT WOS:000347312000001 ER PT J AU Wang, SJ Burtt, K Turkbey, B Choyke, P Summers, RM AF Wang, Shijun Burtt, Karen Turkbey, Baris Choyke, Peter Summers, Ronald M. TI Computer Aided-Diagnosis of Prostate Cancer on Multiparametric MRI: A Technical Review of Current Research SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID CONTRAST-ENHANCED MRI; SUPPORT VECTOR MACHINES; DIFFUSION-WEIGHTED MRI; ENDORECTAL COIL; RANDOMIZED PROSTATE; MUTUAL INFORMATION; SCREENING TRIAL; FOLLOW-UP; DCE-MRI; 3 T AB Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the United States. In this paper, we survey computer aided-diagnosis (CADx) systems that use multiparametric magnetic resonance imaging (MP-MRI) for detection and diagnosis of prostate cancer. We review and list mainstream techniques that are commonly utilized in image segmentation, registration, feature extraction, and classification. The performances of 15 state-of-the-art prostate CADx systems are compared through the area under their receiver operating characteristic curves (AUC). Challenges and potential directions to further the research of prostate CADx are discussed in this paper. Further improvements should be investigated tomake prostate CADx systems useful in clinical practice. C1 [Wang, Shijun; Burtt, Karen; Summers, Ronald M.] NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room 1C224, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural Research Programs of the NIH Clinical Center FX This work was supported by the Intramural Research Programs of the NIH Clinical Center. The authors thank Kristine Evers for her help on the writing of the paper. NR 71 TC 1 Z9 1 U1 2 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 789561 DI 10.1155/2014/789561 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AY0ZR UT WOS:000347323800001 ER PT J AU Lu, DP Chen, YM Xu, LX Lee, LM AF Lu, Dominic P. Chen, Yemeng Xu, Lixian Lee, Leo M. TI Eastern Medicine: From Nutritional Supplements to Cancer Research SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Lu, Dominic P.] Univ Penn, Philadelphia, PA 19104 USA. [Chen, Yemeng] New York Coll Tradit Chinese Med, Mineola, NY 11501 USA. [Xu, Lixian] Fourth Mil Med Univ, Sch Stomatol, Dept Anesthesiol, Xian 710032, Shaanxi, Peoples R China. [Lee, Leo M.] NCI, NIH, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Lu, DP (reprint author), Univ Penn, Philadelphia, PA 19104 USA. EM dominicplu@gmail.com OI Chen, Yemeng/0000-0001-7746-6253 NR 0 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2014 AR 817126 DI 10.1155/2014/817126 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AY1BA UT WOS:000347327300001 ER PT J AU Brodie, BR Pokharel, Y Garg, A Kissling, G Hansen, C Milks, S Cooper, M Mcalhany, C Stuckey, TD AF Brodie, Bruce R. Pokharel, Yashashwi Garg, Ankit Kissling, Grace Hansen, Charles Milks, Sally Cooper, Michael Mcalhany, Christopher Stuckey, Thomas D. TI Very Late Hazard with Stenting versus Balloon Angioplasty for ST-Elevation Myocardial Infarction: A 16-Year Single-Center Experience SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID DRUG-ELUTING STENTS; BARE-METAL STENTS; PERCUTANEOUS CORONARY INTERVENTION; THROMBOSIS; TRIAL AB Objectives: This study compares very late outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) with stenting versus balloon angioplasty (BA). Background: Stenting compared with BA for STEMI improves outcomes at 6-12 months, but comparisons beyond 6-12 months have not been studied. Recent studies have shown that stent thrombosis (ST) continues to increase beyond 3-5 years and may be higher with drug-eluting stents (DES) than bare metal stents (BMS). We hypothesized that there may be a very late hazard with stenting versus BA due to very late ST. Methods: From 1994 to 2010 consecutive patients with STEMI treated with BA (n = 601) or stenting (n = 1,594) were prospectively enrolled in our registry and followed for 1-16 years. Results: Patients treated with BAwere older, were more often female, had more three-vessel disease, and had smaller vessels. Stented patients had trends for less stent/lesion thrombosis (ST/LT) and target vessel (TV) reinfarction at 1 year. In landmark analyses > 1 year, stented patients had more very late ST/LT (6.1% vs. 2.9%, P=0.002) and more TV reinfarction (7.9% vs. 3.1%, P<0.001) which remained significant after adjusting for baseline risk. The greatest differences in very late outcomes were between DES and BA, but there were also significant differences between BMS and BA. Conclusions: There appears to be a very late hazard with stenting versus BA for STEMI. These data should encourage new strategies for prevention of very late ST with both BMS and DES including the development of bio-absorbable polymers and stent platforms. C1 [Brodie, Bruce R.; Milks, Sally; Cooper, Michael; Mcalhany, Christopher; Stuckey, Thomas D.] LeBauer Cardiovasc Res Fdn, Greensboro, NC USA. [Pokharel, Yashashwi; Garg, Ankit; Hansen, Charles] Moses Cone Mem Hosp, Internal Med Residency Program, Greensboro, NC USA. [Kissling, Grace] NIEHS, Res Triangle Pk, NC 27709 USA. RP Brodie, BR (reprint author), 313 Meadowbrook Terrace, Greensboro, NC 27408 USA. EM bbrodie89@gmail.com FU LeBauer Charitable Research Foundation; NIEHS FX Grant sponsor: LeBauer Charitable Research Foundation; Grant sponsor: NIEHS. NR 16 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0896-4327 EI 1540-8183 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD JAN PY 2014 VL 27 IS 1 BP 21 EP 28 DI 10.1111/joic.12082 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX1HE UT WOS:000346697600003 PM 24372979 ER PT J AU Kaler, SG AF Kaler, Stephen G. TI Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment SO JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 10th Meeting of the International-Society-for-Trace-Element-Research-in-Humans (ISTERH) CT 10th International Society for Trace Element Research in Humans (ISTERH) CY NOV 18-22, 2013 CY NOV 18-22, 2013 CL Tokyo, JAPAN CL Tokyo, JAPAN SP Int Soc Trace Element Res Humans DE Menkes disease; ATP7A; Copper; Neurodevelopment; Brain growth ID CANDIDATE GENE; HORN SYNDROME; THERAPY; MUTATION; ENCODES; PLASMA; HAIR AB Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n = 35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation. Published by Elsevier GmbH. C1 NICHD, Sect Translat Neurosci, Program Mol Med, Porter Neurosci Res Ctr 2,NIH, Bethesda, MD 20892 USA. RP Kaler, SG (reprint author), NICHD, Sect Translat Neurosci, Program Mol Med, Porter Neurosci Res Ctr 2,NIH, Bldg 35,Room 2D-971,35A Convent Dr,MSC 3754, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU Intramural NIH HHS [ZIA HD008768-10] NR 31 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0946-672X J9 J TRACE ELEM MED BIO JI J. Trace Elem. Med. Biol. PY 2014 VL 28 IS 4 SI SI BP 427 EP 430 DI 10.1016/j.jtemb.2014.08.008 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AX8AW UT WOS:000347133800015 PM 25281031 ER PT J AU Kuipers, SD Bramham, CR Cameron, HA Fitzsimons, CP Korosi, A Lucassen, PJ AF Kuipers, Sjoukje D. Bramham, Clive R. Cameron, Heather A. Fitzsimons, Carlos P. Korosi, Aniko Lucassen, Paul J. TI Environmental Control of Adult Neurogenesis: From Hippocampal Homeostasis to Behavior and Disease SO NEURAL PLASTICITY LA English DT Editorial Material C1 [Kuipers, Sjoukje D.; Bramham, Clive R.] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway. [Kuipers, Sjoukje D.] Univ Bergen, Dept Biol, N-5020 Bergen, Norway. [Kuipers, Sjoukje D.; Bramham, Clive R.] KG Jebsen Ctr Res Neuropsychiat Disorders, N-5009 Bergen, Norway. [Cameron, Heather A.] NIMH, NIH, Bethesda, MD 20892 USA. [Fitzsimons, Carlos P.; Korosi, Aniko; Lucassen, Paul J.] Univ Amsterdam, Ctr Neurosci, Swammerdam Inst Life Sci SILS, NL-1098 XH Amsterdam, Netherlands. RP Kuipers, SD (reprint author), Univ Bergen, Dept Biomed, N-5009 Bergen, Norway. EM sjoukje.kuipers@biomed.uib.no NR 7 TC 0 Z9 0 U1 2 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2014 AR 808643 DI 10.1155/2014/808643 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AX6TF UT WOS:000347053300001 ER PT J AU Filson, CP Schwartz, K Colt, JS Ruterbusch, J Linehan, WM Chow, WH Miller, DC AF Filson, Christopher P. Schwartz, Kendra Colt, Joanne S. Ruterbusch, Julie Linehan, W. Marston Chow, Wong-Ho Miller, David C. TI Use of nephron-sparing surgery among renal cell carcinoma patients with diabetes and hypertension SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Renal cell carcinoma; Nephrectomy; Diabetes; Hypertension; Physician practice patterns ID RADICAL NEPHRECTOMY; KIDNEY-DISEASE; RISK-FACTORS; CANCER; TRENDS AB Objectives: Nephron-sparing surgery (NSS) is recommended for patients with renal cell carcinoma (RCC) at risk for chronic kidney disease (CKD). We assessed the prevalence of NSS among RCC patients with pre-existing diabetes or hypertension or both, who participated in a population-based epidemiologic RCC study. Materials and methods: Patients with RCC were enrolled in the United States Kidney Cancer Study, a case-control study in the metropolitan areas of Detroit and Chicago from 2002 to 2007. After determining whether patients had diabetes or hypertension or both, we ascertained the proportion of patients from the Detroit site who received NSS. Bivariate and multivariate analyses were performed to evaluate associations between these CKD risk factors and receipt of NSS. Results: We identified 835 patients treated with radical nephrectomy (78%) or NSS (22%) from 2002 to 2007. Among this cohort, 60% had pre-existing diabetes or hypertension or both. Patients with both diabetes and hypertension were more than twice as likely to receive NSS (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.47-3.96). Conversely, patients with only hypertension (OR 1.33, 95% CI 0.92-1.93) or diabetes (OR 0.97, 95% CI 0.92-1.93) were no more likely to receive NSS than patients with neither risk factor. Conclusions: The more frequent utilization of NSS among patients with both diabetes and hypertension suggests growing recognition by urologists of the importance of these risk factors for future development of CKD among patients facing surgical therapy for RCC. However, the concurrent observation that patients with only one of these CKD risk factors did not receive increased utilization of NSS highlights an immediate opportunity to improve the surgical treatment of patients with RCC. Published by Elsevier Inc. C1 [Filson, Christopher P.; Miller, David C.] Univ Michigan, Dept Urol, Div Hlth Serv Res, Ann Arbor, MI 48109 USA. [Schwartz, Kendra; Ruterbusch, Julie] Karmanos Canc Inst, Detroit, MI USA. [Schwartz, Kendra] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Colt, Joanne S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Miller, DC (reprint author), Univ Michigan, Dept Urol, Div Hlth Serv Res, Ann Arbor, MI 48109 USA. EM dcmiller@umich.edu OI Filson, Christopher/0000-0002-9353-871X; Filson, Christopher/0000-0002-8184-7275 FU National Institutes of Health [NIH-N02-CP-11004, NIH-T32-DK007782]; New York Academy of Medicine FX This research was supported by the National Institutes of Health Intramural Research Program (NIH-N02-CP-11004) and Training in Clinical Investigation in Urology grant (NIH-T32-DK007782); and the Edwin Beer Research Fellowship in Urology and Urology-Related Fields from the New York Academy of Medicine to D.C.M. NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2012.09.014 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300017 ER PT J AU Trinh, QD Sun, M Kim, SP Sammon, J Kowalczyk, KJ Friedman, AA Sukumar, S Ravi, P Muhletaler, F Agarwal, PK Shariat, SF Hu, JC Menon, M Karakiewicz, PI AF Quoc-Dien Trinh Sun, Maxine Kim, Simon P. Sammon, Jesse Kowalczyk, Keith J. Friedman, Ariella A. Sukumar, Shyam Ravi, Praful Muhletaler, Fred Agarwal, Piyush K. Shariat, Shahrokh F. Hu, Jim C. Menon, Mani Karakiewicz, Pierre I. TI The impact of hospital volume, residency, and fellowship training on perioperative outcomes after radical prostatectomy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostatic neoplasms; Prostatectomy; Complication; Teaching; Residency; Fellowship ID QUALITY-OF-CARE; SURGICAL-PROCEDURES; TEACHING STATUS; CANCER; COMPLICATIONS; MORBIDITY; MORTALITY; SURGERY; TRENDS AB Objectives: Although high-volume hospitals have been associated with improved outcomes for radical prostatectomy (RP), the association of residency or fellowship teaching institutions or both and this volume-outcome relationship remains poorly described. We examine the effect of teaching status and hospital volume on perioperative RP outcomes. Methods and materials: Within the Nationwide Inpatient Sample, we focused on RPs performed between 2003 and 2007. We tested the rates of prolonged length of stay beyond the median of 3 days, in-hospital mortality, and intraoperative and postoperative complications, stratified according to teaching status. Multivariable logistic regression analyses further adjusted for confounding factors. Results: Overall. 47,100 eligible RPs were identified. Of these. 19,193 cases were performed at non-teaching institutions, 24,006 at residency teaching institutions, and 3,901 at fellowship teaching institutions. Relative to patients treated at non-teaching institutions, patients treated at fellowship teaching institutions were healthier and more likely to hold private insurance. In multivariable analyses, patients treated at residency (OR = 0.92, P = 0.015) and fellowship (OR = 0.82, P = 0.011) teaching institutions were less likely to experience a postoperative complication than patients treated at non-teaching institutions. Patients treated at residency (OR = 0.73, P < 0.001) and fellowship (OR = 0.91, P = 0.045) teaching institutions were less likely to experience a prolonged length of stay. Conclusions: More favorable postoperative complication profile and shorter length of stay should be expected at residency and fellowship teaching institutions following RP. Moreover, postoperative complication rates were lower at fellowship teaching than at residency teaching institutions, despite adjustment for potential confounders. (C) 2014 Elsevier Inc. All rights reserved. C1 [Quoc-Dien Trinh; Sammon, Jesse; Friedman, Ariella A.; Sukumar, Shyam; Ravi, Praful; Muhletaler, Fred; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Quoc-Dien Trinh; Sun, Maxine; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Kim, Simon P.] Mayo Clin, Dept Urol, Rochester, MN USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Agarwal, Piyush K.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Shariat, Shahrokh F.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. RP Trinh, QD (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. EM trinh.qd@gmail.com OI Friedman, Ariella/0000-0002-0709-0008; Agarwal, Piyush/0000-0002-6042-6834 FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX Pierre I. Karakiewicz is partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery, and the University of Montreal Health Centre (CHUM) Foundation. NR 23 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2012.10.008 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300024 ER PT J AU Shuch, B Hofmann, JN Merino, MJ Nix, JW Vourganti, S Linehan, WM Schwartz, K Ruterbusch, JJ Colt, JS Purdue, MP Chow, WH AF Shuch, Brian Hofmann, Jonathan N. Merino, Maria J. Nix, Jeffrey W. Vourganti, Srinivas Linehan, W. Marston Schwartz, Kendra Ruterbusch, Julie J. Colt, Joanne S. Purdue, Mark P. Chow, Wong-Ho TI Pathologic validation of renal cell carcinoma histology in the Surveillance, Epidemiology, and End Results program SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE RCC; SEER Histology; Pathology; Concordance; Accuracy ID RISING INCIDENCE; CANCER; PAPILLARY AB Purpose: The Surveillance, Epidemiology, and End Results (SEER) program is an important epidemiologic research tool to study cancer. No information is available on its pathologic accuracy for renal cell carcinoma (RCC). Methods: Central pathology review was analyzed as a part of the United States Kidney Cancer Study. Cases previously identified through the Detroit SEER registry were reviewed. The sensitivity and specificity, and positive and negative predictive values were calculated for each SEER-assigned subtype, with the central review assignments used as the reference. Results: Of the 498 cases included in this study, 490 (98.5%) were confirmed to be RCC. The overall agreement for histology was 78.2% (K = 0.55); however, individual cases were frequently reclassified. The sensitivity and specificity for SEER-assigned clear cell RCC were 79.1% and 88.1%, respectively, when based solely on the ICD-0-3 morphology code 8310 (n = 310), and 99.2% and 80.5% when 8312 (RCC not otherwise specified; n = 41) was also assumed to be clear cell. Although RCC not otherwise specified is frequently grouped with clear cell, only 78.1% had this histology. Assignments of papillary and chromophobe RCC had comparable sensitivities (73.5% and 72.4%, respectively) and specificities (97.5% and 97.6%). Positive predictive values for clear cell (excluding/including 8312), papillary, and chromophobe RCC were 95.591/93.5%, 85.9%, and 65.6%, respectively. Conclusions: Our findings confirm that nearly all RCC cases are correctly classified in SEER. The positive predictive value was higher for clear cell RCC than for papillary or chromophobe RCC, suggesting that pathologic confirmation may be warranted for studies of non clear cell tumors. Published by Elsevier Inc. C1 [Shuch, Brian; Nix, Jeffrey W.; Vourganti, Srinivas; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Hofmann, Jonathan N.; Colt, Joanne S.; Purdue, Mark P.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Bethesda, MD 20892 USA. [Schwartz, Kendra; Ruterbusch, Julie J.] Wayne State Sch Med, Div Populat Hlth Sci, Detroit, MI USA. RP Shuch, B (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM brian.shuch@nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU NCI FX NCI Intramural funding. NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2012.08.011 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300002 ER PT J AU Vaishampayan, UN Fontana, J Heilbrun, LK Smith, D Heath, E Dickow, B Figg, WD AF Vaishampayan, Ulka N. Fontana, Joseph Heilbrun, Lance K. Smith, Daryn Heath, Elisabeth Dickow, Brenda Figg, William D. TI Phase II trial of bevacizumab and satraplatin in docetaxel-pretreated metastatic castrate-resistant prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Excision repair polymorphism; Prostate cancer; Chemotherapy; Phase II clinical trial ID CELL LUNG-CANCER; SINGLE NUCLEOTIDE POLYMORPHISMS; ENDOTHELIAL GROWTH-FACTOR; INCREASED SURVIVAL; COLORECTAL-CANCER; PLUS PREDNISONE; CHEMOTHERAPY; MITOXANTRONE; COMBINATION; GUIDELINES AB Background: Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has been noted. Methods: Docetaxel-pretreated metastatic castrate-resistant prostate cancer patients with disease progression were eligible. Satraplatin 80 mg/m(2) orally on days 1 to 5, prednisone 5 mg twice daily, and bevacizumab 10 mg/kg on clay 1, and 15 mg/kg on clay 15 were administered in 35-day cycles. Results: Thirty one patients were enrolled. Grade 3 or 4 toxicities were pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. 31% of the patients had a >= 30% decline in prostate-specific antigen. Median time to progression was 7.0 months (90% confidence interval [CI] 4.7-8.5 mo) and median overall survival was 11.2 months (90% CI 9.1-16.4 mo). Polymorphism in the excision repair cross-complementation-1 (ERCC-1) gene was associated with time to progression (hazard ratio = 1.91). A circulating tumor cell count >= 5was moderately prognostic of overall survival (hazard ratio = 1.49) as compared with CTC <5. Conclusions: The combination was tolerable, and revealed promising efficacy in metastatic castrate-resistant prostate cancer. ERCC1 genotype maybe predictive of clinical benefit with platinum-based therapy in metastatic prostate cancer. (C) 2014 Elsevier Inc. All tights reserved. C1 [Vaishampayan, Ulka N.; Fontana, Joseph; Heath, Elisabeth] Wayne State Univ, Dept Med, Dept Oncol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48202 USA. [Heilbrun, Lance K.; Smith, Daryn] Barbara Ann Karmanos Canc Inst, Biostat Core, Detroit, MI USA. [Dickow, Brenda] Barbara Ann Karmanos Canc Inst, Clin Trials Off, Detroit, MI USA. [Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Vaishampayan, UN (reprint author), Wayne State Univ, Dept Med, Dept Oncol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48202 USA. EM vaishamu@karmanos.org RI Figg Sr, William/M-2411-2016; OI Fontana, Joseph/0000-0003-3829-3358 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The views expressed within this paper do not necessarily reflect those of the US Government. NR 27 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2012.11.017 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300033 ER PT J AU Maiti, P Manna, J Veleri, S Frautschy, S AF Maiti, Panchanan Manna, Jayeeta Veleri, Shobi Frautschy, Sally TI Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID HEAT-SHOCK PROTEINS; SYNUCLEIN-INDUCED TOXICITY; APOPTOSIS-INDUCING FACTOR; AMYLOID-BETA-PEPTIDE; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; IN-VIVO; ALZHEIMERS-DISEASE; MEDIATED AUTOPHAGY AB The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell. C1 [Maiti, Panchanan] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. [Manna, Jayeeta] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. [Veleri, Shobi] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Frautschy, Sally] Vet Greater Los Angeles Healthcare Syst, Geriatr Res & Educ Core, Los Angeles, CA 90073 USA. [Frautschy, Sally] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Frautschy, Sally] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Maiti, P (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. EM panchananm@gmail.com; frauthsch@ucle.edu FU Veterans Administration [RX000669, I01 BX001257]; Cure HD Initiative; NIH [R01 (NS41574)]; [NIH RO1AG021975]; [NIH RC1AT006816] FX This work was supported by Veterans Administration (Rehabilitation Grant RX000669 and Merit I01 BX001257), NIH RO1AG021975, NIH RC1AT006816, the Cure HD Initiative, and NIH Grant R01 (NS41574). NR 133 TC 3 Z9 3 U1 4 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 495091 DI 10.1155/2014/495091 PG 14 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AX5SL UT WOS:000346987500001 ER PT J AU Lai, K Boxer, MB Marabotti, A AF Lai, Kent Boxer, Matthew B. Marabotti, Anna TI GALK inhibitors for classic galactosemia SO FUTURE MEDICINAL CHEMISTRY LA English DT Review ID DROSOPHILA-MELANOGASTER MODEL; GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE DEFICIENCY; CHROMATOGRAPHY-MASS SPECTROMETRY; SMALL-MOLECULE INHIBITORS; HUMAN GALACTOKINASE; FLUOROMETRIC METHOD; VERBAL DYSPRAXIA; ACCURATE DOCKING; OXIDATIVE STRESS; OUTCOME SEVERITY AB Classic galactosemia is an inherited metabolic disease for which, at present, no therapy is available apart from galactose-restricted diet. However, the efficacy of the diet is questionable, since it is not able to prevent the insurgence of chronic complications later in life. In addition, it is possible that dietary restriction itself could induce negative side effects. Therefore, there is a need for an alternative therapeutic approach that can avert the manifestation of chronic complications in the patients. In this review, the authors describe the development of a novel class of pharmaceutical agents that target the production of a toxic metabolite, galactose-1-phosphate, considered as the main culprit for the cause of the complications, in the patients. C1 [Lai, Kent] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT 84132 USA. [Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Marabotti, Anna] Univ Salerno, Dept Chem & Biol, I-84084 Fisciano, SA, Italy. RP Marabotti, A (reprint author), Univ Salerno, Dept Chem & Biol, Via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy. EM amarabotti@unisa.it FU NIH/NICHD [1R01HD074844-01]; Galactosemia Foundation; 'Fondi di Ateneo per la Ricerca di Base' (FARB) [ORSA130225] FX This work was supported by research grant 1R01HD074844-01 (NIH/NICHD), another from the Galactosemia Foundation (K Lai), as well as one from 'Fondi di Ateneo per la Ricerca di Base' (FARB) 2013, ORSA130225 (A Marabotti). MB Boxer has a patent issued surrounding ML152. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 91 TC 5 Z9 5 U1 1 U2 9 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PY 2014 VL 6 IS 9 SI SI BP 1003 EP 1015 DI 10.4155/FMC.14.43 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AX1FP UT WOS:000346693700011 PM 25068984 ER PT J AU Magpantay, FMG Riolo, MA de Celles, MD King, AA Rohani, P AF Magpantay, F. M. G. Riolo, M. A. de Celles, M. Domenech King, A. A. Rohani, P. TI EPIDEMIOLOGICAL CONSEQUENCES OF IMPERFECT VACCINES FOR IMMUNIZING INFECTIONS SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE age-structured population models; infectious disease dynamics; imperfect vaccines ID VACCINATION; EFFICACY; MODEL; HETEROGENEITY; PERSISTENCE AB The control of some childhood diseases has proved to be difficult even in countries that maintain high vaccination coverage. This may be due to the use of imperfect vaccines, and there has been much discussion on the different modes by which vaccines might fail. To understand the epidemiological implications of some of these different modes, we performed a systematic analysis of a model based on the standard susceptible-infectious-recovered equations with a vaccinated component that permits vaccine failure in degree ("leakiness"), take ("all-or-nothingness"), and duration (waning of vaccine-derived immunity). The model was first considered as a system of ordinary differential equations and then extended to a system of partial differential equations to accommodate age structure. We derived analytic expressions for the steady states of the system and the final age distributions in the case of homogenous contact rates. The stability of these equilibria are determined by a threshold parameter R-p, a function of the vaccine failure parameters and the coverage p. The value of p for which R-p = 1 yields the critical vaccination ratio, a measure of herd immunity. Using this concept, we can compare vaccines that confer the same level of herd immunity to the population but may fail at the individual level in different ways. For any fixed R-p > 1, the leaky model results in the highest prevalence of infection, while the all-or-nothing and waning models have the same steady state prevalence. The actual composition of a vaccine cannot be determined on the basis of steady state levels alone, but the distinctions can be made by looking at transient dynamics (such as after the onset of vaccination), the mean age of infection, the age distributions at steady state of the infected class, and the effect of age-specific contact rates. C1 [Magpantay, F. M. G.; de Celles, M. Domenech; King, A. A.; Rohani, P.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Riolo, M. A.; King, A. A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [King, A. A.; Rohani, P.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [King, A. A.; Rohani, P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Magpantay, FMG (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM felicigm@umich.edu; mariolo@umich.edu; matthied@umich.edu; kingaa@umich.edu; rohani@umich.edu OI King, Aaron/0000-0001-6159-3207 FU Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center; National Institutes of Health [1R01AI101155] FX This author's work was supported by the Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health, and by a research grant from the National Institutes of Health (1R01AI101155). NR 20 TC 8 Z9 8 U1 0 U2 5 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 EI 1095-712X J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PY 2014 VL 74 IS 6 BP 1810 EP 1830 DI 10.1137/140956695 PG 21 WC Mathematics, Applied SC Mathematics GA AX3NK UT WOS:000346845900005 PM 25878365 ER PT J AU Zhu, XG Zhu, YJ Kim, DW Meltzer, P Cheng, SY AF Zhu, Xuguang Zhu, Yuelin J. Kim, Dong Wook Meltzer, Paul Cheng, Sheue-Yann TI Activation of integrin-ERBB2 signaling in undifferentiated thyroid cancer SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Growth regulation; thyroid cancer; ERBB2; integrins; microarrays; gene expression ID BREAST-CANCER; MOUSE MODEL; BETA GENE; EXPRESSION; HORMONE; GROWTH; ERBB2; FIBRONECTIN; DISEASE; MICE AB Undifferentiated thyroid carcinoma is one of the most aggressive human cancers. Although genetic changes underlying this aggressive cancer remain to be elucidated, RAS mutations have been frequently identified in it. Mice harboring a mutant thyroid hormone receptor Thrb(PV) (Thrb(PV/PV)) spontaneously develop differentiated follicular thyroid carcinoma similar to human thyroid cancer. We recently demonstrated that targeting a RAS mutation (KrasG12D) to the thyroid of Thrb(PV/PV) mice (Thrb(PV/PV)Kras(G12D) mice) promotes initiation and progression of undifferentiated thyroid cancer. To uncover genes destined to drive the aggressive cancer phenotype, we used cDNA microarrays to compare the gene expression profiles of thyroid cells of Kras(G12D) mice and thyroid tumor lesions of Thrb(PV/PV) and Thrb(PV/PV)Kras(G12D) mice. Analyses of microarray data identified 14 upstream regulators that were significantly altered in thyroid tumors of Thrb(PV/PV) and Thrb(PV/PV)Kras(G12D) mice. Most of these genes with altered expression function as key regulators in growth factor-induced signaling. Further analysis identified gene expression profiles of markedly elevated integrin levels, acting as upstream activators to stimulate ERBB2-mediated downstream signaling in thyroid tumors of Thrb(PV/PV)Kras(G12D) mice. The present studies uncovered integrin-activated ERBB2 signaling as one of the mechanisms in synergy between TR beta PV and KRASG12D signaling to promote aggressive tumor growth in undifferentiated thyroid cancer. C1 [Zhu, Xuguang; Kim, Dong Wook; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhu, Yuelin J.; Meltzer, Paul] NCI, Lab Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 37 TC 3 Z9 4 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2014 VL 4 IS 6 BP 776 EP 788 PG 13 WC Oncology SC Oncology GA AX3QZ UT WOS:000346855300014 PM 25520867 ER PT J AU Rahman, M Xie, DW Feldman, HI Go, AS He, J Kusek, JW Lash, J Miller, ER Ojo, A Pan, Q Seliger, SL Steigerwalt, S Townsend, RR AF Rahman, Mahboob Xie, Dawei Feldman, Harold I. Go, Alan S. He, Jiang Kusek, John W. Lash, James Miller, Edgar R., III Ojo, Akinlolu Pan, Qiang Seliger, Stephen L. Steigerwalt, Susan Townsend, Ray R. CA CRIC Study Investigators TI Association Between Chronic Kidney Disease Progression and Cardiovascular Disease: Results from the CRIC Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Self-reported CVD; Progression of CKD; Heart failure ID QUALITY INITIATIVE ADQI; 11TH CONSENSUS CONFERENCE; WORSENING RENAL-FUNCTION; HEART-FAILURE; CARDIORENAL SYNDROME; WORKGROUP STATEMENTS; COMPETING RISK; COHORT; INSUFFICIENCY; PATHOPHYSIOLOGY AB Background and Aims: There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study. Methods: A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either endstage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Results: One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR. Conclusions: Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease. (C) 2014 S. Karger AG, Basel C1 [Rahman, Mahboob] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Xie, Dawei; Feldman, Harold I.; Pan, Qiang; Townsend, Ray R.] Univ Penn, Philadelphia, PA 19104 USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. [He, Jiang] Tulane Univ, New Orleans, LA 70118 USA. [Kusek, John W.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Lash, James] Univ Illinois, Chicago, IL USA. [Miller, Edgar R., III] Johns Hopkins Univ, Baltimore, MD USA. [Ojo, Akinlolu] Univ Michigan, Ann Arbor, MI 48109 USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Steigerwalt, Susan] St Johns Hosp, Renaissance Renal Res Inst, Detroit, MI USA. RP Rahman, M (reprint author), 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Mahboob.Rahman@uhhospitals.org FU National Institute of Diabetes and Digestive and Kidney Diseases [5U01 DK060990, 5U01 DK060984, 5U01 DK06102, 5U01 DK061021, 5U01 DK061028, 5U01 DK60980, 5U01 DK060963, 5U01 DK060902]; Johns Hopkins University [UL1 RR-025005]; University of Maryland [GRCR M01 RR-16500]; Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) [UL1 RR-024989]; University of Michigan [GCRC M01 RR-000042, CTSA UL1 RR-024986]; University of Illinois at Chicago; Center for Clinical and Translational Science [UL1 RR029879]; Tulane/LSU/Charity Hospital General Clinical Research Center [RR-05096]; University of Pennsylvania Clinical and Translational Science Award NIH/NCATS [UL1 TR000003]; Kaiser Permanente NIH/NCRR UCSF-CTSI [UL1 RR-024131, 5K24 DK002651] FX This work was supported by cooperative agreements from National Institute of Diabetes and Digestive and Kidney Diseases (5U01 DK060990, 5U01 DK060984, 5U01 DK06102, 5U01 DK061021, 5U01 DK061028, 5U01 DK60980, 5U01 DK060963, and 5U01 DK060902). Additional support was provided by the following institutional Clinical Translational Science Awards and other National Institutes of Health grants: Johns Hopkins University UL1 RR-025005, University of Maryland GRCR M01 RR-16500, Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989, University of Michigan GCRC M01 RR-000042 and CTSA UL1 RR-024986, University of Illinois at Chicago, Center for Clinical and Translational Science UL1 RR029879 Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096, University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1 TR000003, -and Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131 and 5K24 DK002651. NR 31 TC 5 Z9 7 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2014 VL 40 IS 5 BP 399 EP 407 DI 10.1159/000368915 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AW5YS UT WOS:000346347500002 PM 25401485 ER PT J AU Bass, BP Engel, KB Greytak, SR Moore, HM AF Bass, B. Paige Engel, Kelly B. Greytak, Sarah R. Moore, Helen M. TI A Review of Preanalytical Factors Affecting Molecular, Protein, and Morphological Analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) Tissue How Well Do You Know Your FFPE Specimen? SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; INVASIVE BREAST-CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; MARKER-IMMUNOSTAINING INTENSITY; RAPID MICROWAVE FIXATION; NUCLEAR ANTIGEN PCNA; HUMAN-BRAIN-TISSUE; REAL-TIME PCR; C VIRUS-RNA AB Context.-Formalin fixation and paraffin embedding is a timeless, cost-efficient, and widely adopted method of preserving human tissue biospecimens that has resulted in a substantial reservoir of formalin-fixed, paraffin-embedded blocks that represent both the pathology and preanalytical handling of the biospecimen. This reservoir of specimens is increasingly being used for DNA, RNA, and proteomic analyses. Objective.-To evaluate the impact of preanalytical factors associated with the formalin fixation and paraffin embedding process on downstream morphological and molecular endpoints. Data Sources.-We surveyed the existing literature using the National Cancer Institute's Biospecimen Research Database for published reports investigating the potential influence of preanalytical factors associated with the formalin fixation and paraffin embedding process on DNA, RNA, protein, and morphological endpoints. Conclusions.-Based on the literature evidence, the molecular, proteomic, and morphological endpoints can be altered in formalin-fixed, paraffin-embedded specimens by suboptimal processing conditions. While the direction and magnitude of effects associated with a given preanalytical factor were dependent on the analyte (DNA, RNA, protein, and morphology) and analytical platform, acceptable conditions are highlighted, and a summary of conditions that could preclude analysis is provided. C1 [Bass, B. Paige; Greytak, Sarah R.] Kelly Serv, Kelly Govt Solut Program, Rockville, MD USA. [Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Engel, Kelly B.] Preferred Solut Grp, Arlington, VA USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr,Room 3W422,Mail Stop Code 9728, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov FU Biorepositories and Biospecimen Research Branch of the National Cancer Institute FX This study was supported by the Biorepositories and Biospecimen Research Branch of the National Cancer Institute. NR 162 TC 21 Z9 25 U1 0 U2 11 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PY 2014 VL 138 IS 11 BP 1520 EP 1530 DI 10.5858/arpa.2013-0691-RA PG 11 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AW6NC UT WOS:000346385100017 PM 25357115 ER PT J AU Davenport, TE Shrader, JA McElroy, B Rakocevic, G Dalakas, M Harris-Love, MO AF Davenport, Todd E. Shrader, Joseph A. McElroy, Beverly Rakocevic, Goran Dalakas, Marinos Harris-Love, Michael O. TI Validity of the single limb heel raise test to predict lower extremity disablement in patients with sporadic inclusion body myositis SO DISABILITY AND REHABILITATION LA English DT Article DE Calf; inclusion body myositis; single limb heel raise test; validity; strength ID ANKLE PLANTAR-FLEXION; MUSCLE FUNCTION; ELDERLY-WOMEN; RISE TEST; GAIT; OLDER; AGE; RELIABILITY; PERFORMANCE; STRENGTH AB Purpose: To determine the validity of the single limb heel raise (SLHR) test as a potential screening tool to detect lower extremity disability in patients with sporadic inclusion body myositis (sIBM). Methods: We compared gait speed and fall history between subjects with sIBM who either could complete one SLHR (SLHR group) or could not complete one SLHR. Discriminative validity was established by comparing between group differences in functional measures based on group assignment. Receiver operating characteristics curve analysis was used to determine the predictive validity of completing one repetition on the SLHR test. Spearman correlations were used to determine the association between gait kinematics and number of repetitions achieved on the SLHR test. Results: Forty-three subjects (13 females) were studied. The SLHR group (n = 21) showed significantly greater gait speed (p<0.001) and decreased gait aid use (p<0.05) compared to the no SLHR group (n = 22). SLHR cut scores of 1, 20, and 22 repetitions maximized positive likelihood ratios (+LR) for the ability to walk at 54.9 (+LR. 2.2), 63.2 (+LR. 9.5), and 73.1 m/min (+LR. 5.0), respectively. Conclusion: The SLHR test demonstrates adequate discriminative and predictive validity as a screening tool for lower extremity disablement in patients with sIBM. C1 [Davenport, Todd E.] Univ Pacific, Dept Phys Therapy, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA 95211 USA. [Shrader, Joseph A.; Harris-Love, Michael O.] NIH, Dept Rehabil Med, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [McElroy, Beverly] NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. [Rakocevic, Goran; Dalakas, Marinos] Thomas Jefferson Univ, Neuromuscular Div, Philadelphia, PA 19107 USA. [Harris-Love, Michael O.] Vet Affairs Med Ctr, Dept Vet Affairs, Washington, DC 20422 USA. [Harris-Love, Michael O.] George Washington Univ, Sch Med & Hlth Sci, Program Phys Therapy, Washington, DC 20052 USA. RP Harris-Love, MO (reprint author), DC Vet Affairs Med Ctr, Dept Vet Affairs, Washington, DC 20422 USA. EM Michael.Harris-Love@va.gov RI Harris-Love, Michael/J-1359-2014 OI Harris-Love, Michael/0000-0002-1842-3269 NR 33 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-8288 EI 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2014 VL 36 IS 26 BP 2270 EP 2277 DI 10.3109/09638288.2014.904447 PG 8 WC Rehabilitation SC Rehabilitation GA AW4MS UT WOS:000346255900011 PM 24678993 ER PT J AU Simpson, EA Husband, HL Yee, K Fullerton, A Jakobsen, KV AF Simpson, Elizabeth A. Husband, Haley L. Yee, Krysten Fullerton, Alison Jakobsen, Krisztina V. TI Visual Search Efficiency Is Greater for Human Faces Compared to Animal Faces SO EXPERIMENTAL PSYCHOLOGY LA English DT Article DE face detection; attention; visual search; search efficiency; eye tracking; human face; animal faces ID HIGH-LEVEL POP; SELECTIVE ATTENTION; PERCEPTUAL LOAD; EVOLVED MODULE; STIMULUS; FEAR; CAPTURE; THREAT; INFORMATION; SIMILARITY AB The Animate Monitoring Hypothesis proposes that humans and animals were the most important categories of visual stimuli for ancestral humans to monitor, as they presented important challenges and opportunities for survival and reproduction; however, it remains unknown whether animal faces are located as efficiently as human faces. We tested this hypothesis by examining whether human, primate, and mammal faces elicit similarly efficient searches, or whether human faces are privileged. In the first three experiments, participants located a target (human, primate, or mammal face) among distractors (non-face objects). We found fixations on human faces were faster and more accurate than fixations on primate faces, even when controlling for search category specificity. A final experiment revealed that, even when task-irrelevant, human faces slowed searches for non-faces, suggesting some bottom-up processing may be responsible for the human face search efficiency advantage. C1 [Simpson, Elizabeth A.] Univ Parma, I-43100 Parma, Italy. [Simpson, Elizabeth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Poolesville, MD USA. [Husband, Haley L.; Yee, Krysten; Fullerton, Alison; Jakobsen, Krisztina V.] James Madison Univ, Harrisonburg, VA 22807 USA. RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 16701 Elmer Sch Rd, Dickerson, MD 20842 USA. EM simpsonea@mail.nih.gov OI Simpson, Elizabeth/0000-0003-2715-2533 FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [P01 HD064653]; PHS HHS [NICHD P01HD064653-01] NR 68 TC 4 Z9 4 U1 2 U2 8 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1618-3169 EI 2190-5142 J9 EXP PSYCHOL JI Exp. Psychol. PY 2014 VL 61 IS 6 BP 439 EP 456 DI 10.1027/1618-3169/a000263 PG 18 WC Psychology, Experimental SC Psychology GA AW5JQ UT WOS:000346312100002 PM 24962122 ER PT J AU Aurioles-Garibay, A Hernandez-Andrade, E Romero, R Garcia, M Qureshi, F Jacques, SM Ahn, H Yeo, L Chaiworapongsa, T Hassan, SS AF Aurioles-Garibay, Alma Hernandez-Andrade, Edgar Romero, Roberto Garcia, Maynor Qureshi, Faisal Jacques, Suzanne M. Ahn, Hyunyoung Yeo, Lami Chaiworapongsa, Tinnakorn Hassan, Sonia S. TI Presence of an Umbilical Artery Notch in Monochorionic/Monoamniotic Twins SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE Cord entanglement; Fetal hypoxia; Umbilical cord knot; Doppler velocimetry; Fetal surveillance ID INTRAUTERINE GROWTH RESTRICTION; VELOCITY WAVE-FORMS; FLOW DOPPLER ULTRASONOGRAPHY; IMPROVED PERINATAL SURVIVAL; MONOAMNIOTIC TWINS; CORD ENTANGLEMENT; SONOGRAPHIC DIAGNOSIS; ANTENATAL MANAGEMENT; TRANSFUSION SYNDROME; CASE SERIES AB Objective: To examine the association between an umbilical artery notch and fetal deterioration in monochorionic/monoamniotic (MC/MA) twins. Methods: Six MC/MA twin pregnancies were admitted at 24-28 weeks of gestation for close fetal surveillance until elective delivery at 32 weeks or earlier in the presence of signs of fetal deterioration. Ultrasound (US) examinations were performed twice weekly. The presence of cord entanglement, umbilical artery notch, abnormal Doppler parameters, a non-reassuring fetal heart rate pattern, or an abnormal fetal biophysical profile were evaluated. Results: Umbilical cord entanglement was observed on US in all pregnancies. The presence of an umbilical artery notch was noted in four out of six pregnancies and in two of them an umbilical artery notch was seen in both twins. The umbilical artery pulsatility index was normal in all fetuses. Doppler parameters of the middle cerebral artery and ductus venosus, fetal biophysical profile and fetal heart rate monitoring remained normal until delivery in all pregnancies. All neonates experienced morbidity related to prematurity; however, all were discharged home in good condition. Conclusion: The presence of an umbilical artery notch and cord entanglement, without other signs of fetal deterioration, are not indicative of an adverse perinatal outcome. (C) 2014 S. Karger AG, Basel. C1 [Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Garcia, Maynor; Qureshi, Faisal; Jacques, Suzanne M.; Ahn, Hyunyoung; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD NIH DHHS, Perinatol Res Branch, Bethesda, MD USA. [Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Garcia, Maynor; Ahn, Hyunyoung; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Dept Pathol, Harper Univ Hosp, Detroit, MI 48202 USA. [Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Department of Health and Human Services (NICHD/NIH); NICHD; NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH), and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 53 TC 3 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 EI 1421-9964 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PY 2014 VL 36 IS 4 BP 305 EP 311 DI 10.1159/000361020 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW4FP UT WOS:000346236900007 PM 25060062 ER PT J AU van Leyen, K Holman, TR Maloney, DJ AF van Leyen, Klaus Holman, Theodore R. Maloney, David J. TI The potential of 12/15-lipoxygenase inhibitors in stroke therapy SO FUTURE MEDICINAL CHEMISTRY LA English DT Article DE edema; eicosanoid; hemorrhage; ischemia; lipoxygenase; oxidative stress; stroke; tissue plasminogen activator ID SPONGE-DERIVED TERPENOIDS; SELECTIVE INHIBITORS; MAMMALIAN 15-LIPOXYGENASE; LIPOXYGENASE INHIBITORS; DISCOVERY; 15-HUMAN; 12-HUMAN C1 [van Leyen, Klaus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. [Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP van Leyen, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu FU US NIH [R01NS081180, R21NS087165] FX Financial support through the US NIH (R01NS081180 to TR Holman and R21NS087165 to K van Leyen) is gratefully acknowledged. Patents for LOXBlock-1 and for ML351 have been applied for. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 20 TC 1 Z9 1 U1 1 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PY 2014 VL 6 IS 17 BP 1853 EP 1855 DI 10.4155/fmc.14.129 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AW5TS UT WOS:000346337300002 PM 25495979 ER PT J AU Ericsen, AJ Starrett, GJ Greene, JM Lauck, M Raveendran, M Deiros, DR Mohns, MS Vince, N Cain, BT Pham, NH Weinfurter, JT Bailey, AL Budde, ML Wiseman, RW Gibbs, R Muzny, D Friedrich, TC Rogers, J O'Connor, DH AF Ericsen, Adam J. Starrett, Gabriel J. Greene, Justin M. Lauck, Michael Raveendran, Muthuswamy Deiros, David Rio Mohns, Mariel S. Vince, Nicolas Cain, Brian T. Ngoc H Pham Weinfurter, Jason T. Bailey, Adam L. Budde, Melisa L. Wiseman, Roger W. Gibbs, Richard Muzny, Donna Friedrich, Thomas C. Rogers, Jeffrey O'Connor, David H. TI Whole genome sequencing of SIV-infected macaques identifies candidate loci that may contribute to host control of virus replication SO GENOME BIOLOGY LA English DT Article ID MAURITIAN CYNOMOLGUS MACAQUES; T-CELL RESPONSES; HIGHLY PATHOGENIC SIV; IMMUNE-RESPONSES; HIV-1 INFECTION; MACACA-FASCICULARIS; VIRAL LOAD; SEX; HAPLOTYPES; VACCINE AB Background: A small percentage of human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected macaques control virus replication without antiretroviral treatment. The major determinant of this control is host expression of certain major histocompatibility complex alleles. However, this association is incompletely penetrant, suggesting that additional loci modify the major histocompatibility complex's protective effect. Here, to identify candidate control-modifying loci, we sequence the genomes of 12 SIV-infected Mauritian cynomolgus macaques that experienced divergent viral load set points despite sharing the protective M1 major histocompatibility complex haplotype. Results: Our genome-wide analysis of haplotype-level variation identifies seven candidate control-modifying loci on chromosomes 2, 3, 7, 8, 9, 10, and 14. The highest variant density marks the candidate on chromosome 7, which is the only control-modifying locus to comprise genes with known immunological function. Upon closer inspection, we found an allele for one of these genes, granzyme B, to be enriched in M1(+) controllers. Given its established role as a cytotoxic effector molecule that participates in CD8-mediated killing of virus-infected cells, we test the role of variation within gzmb in modifying SIV control by prospectively challenging M1(+) granzyme B-defined macaques. Conclusions: Our study establishes a framework for using whole genome sequencing to identify haplotypes that may contribute to complex clinical phenotypes. Further investigation into the immunogenetics underlying spontaneous HIV control may contribute to the rational design of a vaccine that prevents acquired immune deficiency syndrome. C1 [Ericsen, Adam J.; Starrett, Gabriel J.; Greene, Justin M.; Lauck, Michael; Mohns, Mariel S.; Cain, Brian T.; Ngoc H Pham; Bailey, Adam L.; Budde, Melisa L.; Wiseman, Roger W.; O'Connor, David H.] Univ Wisconsin, Dept Pathol, Madison, WI 53705 USA. [Ericsen, Adam J.] Univ Wisconsin, Virol Training Program, Madison, WI 53705 USA. [Raveendran, Muthuswamy; Deiros, David Rio; Gibbs, Richard; Muzny, Donna; Rogers, Jeffrey] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Weinfurter, Jason T.; Friedrich, Thomas C.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. [Vince, Nicolas] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. [Vince, Nicolas] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Friedrich, Thomas C.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol, Madison, WI 53705 USA. EM doconnor@primate.wisc.edu OI Weinfurter, Jason/0000-0001-8076-2598; Friedrich, Thomas/0000-0001-9831-6895; Ericsen, Adam/0000-0003-4176-8270 FU National Institutes of Health [R01 AI077376, R01 AI084787, T32 AI078985]; National Center for Research Resources, a component of the National Institutes of Health [P51 RR000167]; [RR15459-01]; [RR020141-01] FX We would like to thank Matthew Reynolds, Jorge Dinis, and Karl Broman for thoughtful discussions. We acknowledge the staff of the Wisconsin National Primate Research Center's Animal Services and Scientific Protocol Implementation Units for their expertise and assistance with this study. This research was supported by National Institutes of Health grants R01 AI077376, awarded to David H O'Connor, R01 AI084787, awarded to Thomas C Friedrich and David H O'Connor, and T32 AI078985 awarded to Adam J Ericsen. This work was conducted at facilities supported in part by grant number P51 RR000167 from the National Center for Research Resources, a component of the National Institutes of Health. Additionally, work for the manuscript was conducted in a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. NR 56 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 11 AR 478 DI 10.1186/s13059-014-0478-z PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XA UT WOS:000346607300001 PM 25418588 ER PT J AU Jiang, XF Peery, A Hall, B Sharma, A Chen, XG Waterhouse, RM Komissarov, A Riehle, MM Shouche, Y Sharakhova, MV Lawson, D Pakpour, N Arensburger, P Davidson, VLM Eiglmeier, K Emrich, S George, P Kennedy, RC Mane, SP Maslen, G Oringanje, C Qi, YM Settlage, R Tojo, M Tubio, JMC Unger, MF Wang, B Vernick, KD Ribeiro, JC James, AA Michel, K Riehle, MA Luckhart, S Sharakhov, IV Tu, ZJ AF Jiang, Xiaofang Peery, Ashley Hall, Brantley Sharma, Atashi Chen, Xiao-Guang Waterhouse, Robert M. Komissarov, Aleksey Riehle, Michelle M. Shouche, Yogesh Sharakhova, Maria V. Lawson, Dan Pakpour, Nazzy Arensburger, Peter Davidson, Victoria L. M. Eiglmeier, Karin Emrich, Scott George, Phillip Kennedy, Ryan C. Mane, Shrinivasrao P. Maslen, Gareth Oringanje, Chioma Qi, Yumin Settlage, Robert Tojo, Marta Tubio, Jose M. C. Unger, Maria F. Wang, Bo Vernick, Kenneth D. Ribeiro, Josem C. James, Anthony A. Michel, Kristin Riehle, Michael A. Luckhart, Shirley Sharakhov, Igor V. Tu, Zhijian TI Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi SO GENOME BIOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM; CHROMOSOMAL REARRANGEMENT; INVERSION POLYMORPHISMS; NUCLEAR LAMINS; AEDES-AEGYPTI; WEB SERVER; IN-SILICO; RNA-SEQ; GENE; EVOLUTION AB Background: Anopheles stephensi is the key vector of malaria throughout the Indian subcontinent and Middle East and an emerging model for molecular and genetic studies of mosquito-parasite interactions. The type form of the species is responsible for the majority of urban malaria transmission across its range. Results: Here, we report the genome sequence and annotation of the Indian strain of the type form of An. stephensi. The 221 Mb genome assembly represents more than 92% of the entire genome and was produced using a combination of 454, Illumina, and PacBio sequencing. Physical mapping assigned 62% of the genome onto chromosomes, enabling chromosome-based analysis. Comparisons between An. stephensi and An. gambiae reveal that the rate of gene order reshuffling on the X chromosome was three times higher than that on the autosomes. An. stephensi has more heterochromatin in pericentric regions but less repetitive DNA in chromosome arms than An. gambiae. We also identify a number of Y-chromosome contigs and BACs. Interspersed repeats constitute 7.1% of the assembled genome while LTR retrotransposons alone comprise more than 49% of the Y contigs. RNA-seq analyses provide new insights into mosquito innate immunity, development, and sexual dimorphism. Conclusions: The genome analysis described in this manuscript provides a resource and platform for fundamental and translational research into a major urban malaria vector. Chromosome-based investigations provide unique perspectives on Anopheles chromosome evolution. RNA-seq analysis and studies of immunity genes offer new insights into mosquito biology and mosquito-parasite interactions. C1 [Jiang, Xiaofang; Hall, Brantley; Sharakhov, Igor V.; Tu, Zhijian] Virginia Tech, Program Genet Bioinformat & Computat Biol, Blacksburg, VA 24061 USA. [Jiang, Xiaofang; Hall, Brantley; Qi, Yumin; Tu, Zhijian] Virginia Tech, Dept Biochem, Blacksburg, VA USA. [Peery, Ashley; Sharma, Atashi; Sharakhova, Maria V.; George, Phillip; Sharakhov, Igor V.] Virginia Tech, Dept Entomol, Blacksburg, VA USA. [Chen, Xiao-Guang] Southern Med Univ, Dept Pathogen Biol, Guangzhou, Guangdong, Peoples R China. [Waterhouse, Robert M.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Waterhouse, Robert M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Waterhouse, Robert M.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Waterhouse, Robert M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Komissarov, Aleksey] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199034, Russia. [Komissarov, Aleksey] Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. [Riehle, Michelle M.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Shouche, Yogesh; Maslen, Gareth] Pune Univ Campus, Natl Ctr Cell Sci, Pune, Maharashtra, India. [Lawson, Dan] European Bioinformat Inst, Mol Biol Lab, Cambridge CB10 1SD, England. [Pakpour, Nazzy; Wang, Bo; Luckhart, Shirley] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Arensburger, Peter] Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. [Davidson, Victoria L. M.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. [Eiglmeier, Karin; Vernick, Kenneth D.; Michel, Kristin] Inst Pasteur, Dept Parasitol & Mycol, Unit Insect Vector Genet & Genom, Paris, France. [Eiglmeier, Karin; Vernick, Kenneth D.; Michel, Kristin] CNRS, Unit Hosts, Vectors & Pathogens URA3012, Paris, France. [Emrich, Scott] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. [Kennedy, Ryan C.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Mane, Shrinivasrao P.] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA. [Oringanje, Chioma; Tojo, Marta; Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. [Settlage, Robert] Univ Santiago de Compostela, Inst Invest Sanitarias, Sch Med CIMUS, Santiago De Compostela, Spain. [Tubio, Jose M. C.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Unger, Maria F.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Ribeiro, Josem C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD USA. [James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. [James, Anthony A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. RP Sharakhov, IV (reprint author), Virginia Tech, Program Genet Bioinformat & Computat Biol, Blacksburg, VA 24061 USA. EM igor@vt.edu; jaketu@vt.edu RI Tubio, Jose/H-5076-2015; Waterhouse, Robert/A-1858-2010; Komissarov, Aleksey/A-3594-2009 OI Tubio, Jose/0000-0003-3540-2459; Waterhouse, Robert/0000-0003-4199-9052; Ribeiro, Jose/0000-0002-9107-0818; Komissarov, Aleksey/0000-0001-6981-7316 FU Fralin Life Science Institute; Virginia Experimental Station; NIH [AI77680, AI105575, AI094289, AI099528, AI29746, AI095842, AI073745, AI080799, AI078183, AI042361, AI073685]; Institute for Critical Technology and Applied Science; NSF award [0850198]; Marie Curie International Outgoing Fellowship [PIOF-GA-2011-303312]; GDUPS; NSF [CNS-0960081]; Department of Biotechnology, Government of India FX This work is supported by the Fralin Life Science Institute and the Virginia Experimental Station, and by NIH grants AI77680 and AI105575 to ZT, AI094289 and AI099528 to IVS, AI29746 to AAJ, AI095842 to KM, AI073745 to MAR, AI080799 and AI078183 to SL, and AI042361 and AI073685 to KDV. AP and IVS are supported in part by the Institute for Critical Technology and Applied Science and the NSF award 0850198. RMW is supported by Marie Curie International Outgoing Fellowship PIOF-GA-2011-303312. XC is supported by GDUPS (2009). This work was also supported in part by NSF grant CNS-0960081 and the HokieSpeed and BlueRidge supercomputers at Virginia Tech. YS thanks the Department of Biotechnology, Government of India for the financial support. Drew Cocrane provided assistance with in situ hybridization. NR 98 TC 24 Z9 27 U1 2 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 9 AR 459 DI 10.1186/s13059-014-0459-2 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9WA UT WOS:000346604700012 PM 25244985 ER PT J AU Lee, H McManus, CJ Cho, DY Eaton, M Renda, F Somma, MP Cherbas, L May, G Powell, S Zhang, DY Zhan, LJ Resch, A Andrews, J Celniker, SE Cherbas, P Przytycka, TM Gatti, M Oliver, B Graveley, B MacAlpine, D AF Lee, Hangnoh McManus, C. Joel Cho, Dong-Yeon Eaton, Matthew Renda, Fioranna Somma, Maria Patrizia Cherbas, Lucy May, Gemma Powell, Sara Zhang, Dayu Zhan, Lijun Resch, Alissa Andrews, Justen Celniker, Susan E. Cherbas, Peter Przytycka, Teresa M. Gatti, Maurizio Oliver, Brian Graveley, Brenton MacAlpine, David TI DNA copy number evolution in Drosophila cell lines SO GENOME BIOLOGY LA English DT Article ID DOSAGE COMPENSATION; RNA-SEQ; CHROMOSOMAL INSTABILITY; STRUCTURAL VARIATION; NEXT-GENERATION; GENE-EXPRESSION; HUMAN GENOME; S2 CELLS; MELANOGASTER; ANEUPLOIDY AB Background: Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles. Results: Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167). Conclusion: Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis. C1 [Lee, Hangnoh; Oliver, Brian] NIDDK, NIH, Bethesda, MD 20892 USA. [McManus, C. Joel; May, Gemma; Zhan, Lijun; Resch, Alissa; Graveley, Brenton] Univ Connecticut, Ctr Hlth, Inst Syst Genom, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Cho, Dong-Yeon; Przytycka, Teresa M.] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. [Eaton, Matthew; Powell, Sara; MacAlpine, David] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA. [Renda, Fioranna; Somma, Maria Patrizia; Gatti, Maurizio] Univ Roma La Sapienza, CNR, IBPM, I-00185 Rome, Italy. [Renda, Fioranna; Somma, Maria Patrizia; Gatti, Maurizio] Univ Roma La Sapienza, Dipartimento Biol & Biotecnol, I-00185 Rome, Italy. [Cherbas, Lucy; Zhang, Dayu; Andrews, Justen; Cherbas, Peter] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA. [Zhang, Dayu] Zhejiang A&F Univ, Sch Agr & Food Sci, Linan 311300, Zhejiang, Peoples R China. RP Oliver, B (reprint author), NIDDK, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM briano@helix.nih.gov; graveley@uchc.edu; david.macalpine@duke.edu RI McManus, Joel/S-3104-2016; OI McManus, Joel/0000-0002-6605-2642; Graveley, Brenton/0000-0001-5777-5892; Gatti, Maurizio/0000-0003-3777-300X FU National Human Genome Research Institute modENCODE Project [U01 HG004271, HG004279]; Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG10793]; Intramural Research Programs of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases; National Library of Medicine FX We thank modENCODE and members of the Gatti, McManus and Przytycka labs for useful discussions; Valentina Boeva, Can Alkan, and Dave Sturgill for help on copy number and splicing analyses; Jeremy Sandler, Ben Booth and Joe Carlson for assistance with RNA-Seq analysis; and Allen Gibbs, Tim Westwood, and Yu Zhang for insightful comments. This work was supported by the National Human Genome Research Institute modENCODE Project (U01 HG004271 to SEC and HG004279 to DMM), Associazione Italiana per la Ricerca sul Cancro (AIRC, IG10793) to MG, and the Intramural Research Programs of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (BO) and National Library of Medicine (TP). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH, Bethesda, MD. Certain commercial equipment, instruments, or materials are identified in this document. Such identification does not imply recommendation or endorsement by NIH. NR 106 TC 16 Z9 16 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 8 AR R70 DI 10.1186/gb-2014-15-8-r70 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9UU UT WOS:000346604100001 PM 25262759 ER PT J AU Scott, JG Warren, WC Beukeboom, LW Bopp, D Clark, AG Giers, SD Hediger, M Jones, AK Kasai, S Leichter, CA Li, M Meisel, RP Minx, P Murphy, TD Nelson, DR Reid, WR Rinkevich, FD Robertson, HM Sackton, TB Sattelle, DB Thibaud-Nissen, F Tomlinson, C van de Zande, L Walden, KKO Wilson, RK Liu, NN AF Scott, Jeffrey G. Warren, Wesley C. Beukeboom, Leo W. Bopp, Daniel Clark, Andrew G. Giers, Sarah D. Hediger, Monika Jones, Andrew K. Kasai, Shinji Leichter, Cheryl A. Li, Ming Meisel, Richard P. Minx, Patrick Murphy, Terence D. Nelson, David R. Reid, William R. Rinkevich, Frank D. Robertson, Hugh M. Sackton, Timothy B. Sattelle, David B. Thibaud-Nissen, Francoise Tomlinson, Chad van de Zande, Louis Walden, Kimberly K. O. Wilson, Richard K. Liu, Nannan TI Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment SO GENOME BIOLOGY LA English DT Article ID BIASED GENE-EXPRESSION; ACETYLCHOLINE-RECEPTOR SUBUNITS; IONOTROPIC GLUTAMATE RECEPTORS; MULTIPLE SEQUENCE ALIGNMENT; DROSOPHILA-MELANOGASTER; MAXIMUM-LIKELIHOOD; LINKAGE GROUPS; INSECTICIDE RESISTANCE; CHEMOSENSORY RECEPTORS; ANTIMICROBIAL PEPTIDE AB Background: Adult house flies, Musca domestica L., are mechanical vectors of more than 100 devastating diseases that have severe consequences for human and animal health. House fly larvae play a vital role as decomposers of animal wastes, and thus live in intimate association with many animal pathogens. Results: We have sequenced and analyzed the genome of the house fly using DNA from female flies. The sequenced genome is 691 Mb. Compared with Drosophila melanogaster, the genome contains a rich resource of shared and novel protein coding genes, a significantly higher amount of repetitive elements, and substantial increases in copy number and diversity of both the recognition and effector components of the immune system, consistent with life in a pathogen-rich environment. There are 146 P450 genes, plus 11 pseudogenes, in M. domestica, representing a significant increase relative to D. melanogaster and suggesting the presence of enhanced detoxification in house flies. Relative to D. melanogaster, M. domestica has also evolved an expanded repertoire of chemoreceptors and odorant binding proteins, many associated with gustation. Conclusions: This represents the first genome sequence of an insect that lives in intimate association with abundant animal pathogens. The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, and for exploring the basic biology of this important pest. The genome of this species will also serve as a close out-group to Drosophila in comparative genomic studies. C1 [Scott, Jeffrey G.; Kasai, Shinji; Leichter, Cheryl A.; Rinkevich, Frank D.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA. [Warren, Wesley C.; Minx, Patrick; Tomlinson, Chad; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Beukeboom, Leo W.; van de Zande, Louis] Univ Groningen, Ctr Ecol & Evolutionary Studies, NL-9747 Groningen, Netherlands. [Bopp, Daniel; Hediger, Monika] Univ Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland. [Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. [Giers, Sarah D.; Robertson, Hugh M.; Walden, Kimberly K. O.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. [Jones, Andrew K.] Oxford Brookes Univ, Fac Hlth & Life Sci, Dept Biol & Med Sci, Oxford OX3 0BP, England. [Li, Ming; Reid, William R.; Liu, Nannan] Auburn Univ, Dept Entomol & Plant Pathol, Auburn, AL 36849 USA. [Meisel, Richard P.] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. [Murphy, Terence D.; Thibaud-Nissen, Francoise] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, DHHS, Bethesda, MD 20892 USA. [Nelson, David R.] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. [Sackton, Timothy B.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02139 USA. [Sattelle, David B.] UCL, Wolfson Inst Biomed Res, Dept Med, London WC1E 6BT, England. RP Scott, JG (reprint author), Cornell Univ, Dept Entomol, Comstock Hall, Ithaca, NY 14853 USA. EM jgs5@cornell.edu RI Li, Ming/F-4413-2016; OI Sackton, Timothy/0000-0003-1673-9216; Meisel, Richard/0000-0002-7362-9307 FU NIH-NHGRI [5U54HG00307907, NYC-139416, S-1030] FX We thank the production sequencing group of The Genome Institute at Washington University for library construction, sequencing and data curation. This work was supported by NIH-NHGRI grant 5U54HG00307907 to RKW, Hatch Project NYC-139416 to JGS and multistate project S-1030 to JGS. NR 131 TC 44 Z9 44 U1 7 U2 30 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 10 AR 466 DI 10.1186/s13059-014-0466-3 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9WH UT WOS:000346605500001 PM 25315136 ER PT J AU Wang, RH Lahusen, TJ Chen, Q Xu, XL Jenkins, LMM Leo, E Fu, HQ Aladjem, M Pommier, Y Appella, E Deng, CX AF Wang, Rui-Hong Lahusen, Tyler J. Chen, Qiang Xu, Xiaoling Jenkins, Lisa M. Miller Leo, Elisabetta Fu, Haiqing Aladjem, Mirit Pommier, Yves Appella, Ettore Deng, Chu-Xia TI SIRT1 Deacetylates TopBP1 and Modulates Intra-S-Phase Checkpoint and DNA Replication Origin Firing SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE SIRT1; TopBP1; Intra-S-phase checkpoint; DNA replication fork; Genetic stability ID NIJMEGEN BREAKAGE SYNDROME; POLY(ADP-RIBOSE) POLYMERASE 1; PROMOTES CELL-SURVIVAL; DAMAGE RESPONSE; GENETIC INSTABILITY; MAMMALIAN SIRTUINS; GENOME STABILITY; BRCA1; MICE; PROTEIN AB SIRT1, the mammalian homolog of yeast Sir2, is a founding member of a family of 7 protein and histone deacetylases that are involved in numerous biological functions. Previous studies revealed that SIRT1 deficiency results in genome instability, which eventually leads to cancer formation, yet the underlying mechanism is unclear. To investigate this, we conducted a proteomics study and found that SIRT1 interacted with many proteins involved in replication fork protection and origin firing. We demonstrated that loss of SIRT1 resulted in increased replication origin firing, asymmetric fork progression, defective intra-S-phase checkpoint, and chromosome damage. Mechanistically, SIRT1 deacetylates and affects the activity of TopBP1, which plays an essential role in DNA replication fork protection and replication origin firing. Our study demonstrated that ectopic over-expression of the deacetylated form of TopBP1 in SIRT1 mutant cells repressed replication origin firing, while the acetylated form of TopBP1 lost this function. Thus, SIRT1 acts upstream of TopBP1 and plays an essential role in maintaining genome stability by modulating DNA replication fork initiation and the intra-S-phase cell cycle checkpoint. C1 [Wang, Rui-Hong; Lahusen, Tyler J.; Chen, Qiang; Xu, Xiaoling; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Jenkins, Lisa M. Miller; Appella, Ettore] NIH, Cell Biol Lab, Bethesda, MD 20892 USA. [Leo, Elisabetta; Fu, Haiqing; Aladjem, Mirit; Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Wang, Rui-Hong; Xu, Xiaoling; Deng, Chu-Xia] Univ Macau, Fac Hlth Sci, Macao, Peoples R China. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute, National Institutes of Health, USA; Faculty of Health Sciences, University of Macau FX We thank the members of the Deng lab for critical review of the manuscript. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, National Institutes of Health, USA, and by Faculty of Health Sciences, University of Macau. NR 58 TC 7 Z9 7 U1 1 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2014 VL 10 IS 10 BP 1193 EP 1202 DI 10.7150/ijbs.11066 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AW7FI UT WOS:000346429700011 PM 25516717 ER PT J AU Rosenberg, SA AF Rosenberg, Steven A. TI Curative Potential of Cell Transfer Immunotherapy for Cancer SO ONCOLOGIST LA English DT Meeting Abstract C1 [Rosenberg, Steven A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2014 VL 19 SU 1 MA 4 BP S2 EP S2 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400005 ER PT J AU Girones, R Carratala, A Calgua, B Calvo, M Rodriguez-Manzano, J Emerson, S AF Girones, Rosina Carratala, Anna Calgua, Byron Calvo, Miquel Rodriguez-Manzano, Jesus Emerson, Suzanne TI Chlorine inactivation of hepatitis E virus and human adenovirus 2 in water SO JOURNAL OF WATER AND HEALTH LA English DT Article DE chlorine; disinfection; HAdV 2; HEV; sewage; water ID MURINE NOROVIRUS; DRINKING-WATER; A VIRUS; POLYOMAVIRUSES; DISINFECTION; QUALITY; CELLS; ASSAY AB Hepatitis E virus (HEV) is transmitted via the fecal-oral route and has been recognized as a common source of large waterborne outbreaks involving contaminated water in developing countries. Thus, there is the need to produce experimental data on the disinfection kinetics of HEV by chlorine in water samples with diverse levels of fecal contamination. Here, the inactivation of HEV and human adenovirus C serotype 2 (HAdV2), used as a reference virus, was monitored using immunofluorescence and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. HEV has been shown to be susceptible to chlorine disinfection and presented equivalent kinetics to human adenoviruses. The C(t) values observed for a 2-log reduction of HEV were 0.41 in buffered demand-free water and 11.21 mg/L x min in the presence of 1% sewage. The results indicate that the inactivation kinetics of HEV and HAdV2 are equivalent and support the use of chlorine disinfection as an effective strategy to control HEV waterborne transmission. C1 [Girones, Rosina; Carratala, Anna; Calgua, Byron; Rodriguez-Manzano, Jesus] Univ Barcelona, Fac Biol, Dept Microbiol, Barcelona 08028, Catalonia, Spain. [Calvo, Miquel] Univ Barcelona, Dept Biostat, E-08028 Barcelona, Spain. [Girones, Rosina; Emerson, Suzanne] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Girones, R (reprint author), Univ Barcelona, Fac Biol, Dept Microbiol, Avd Diagonal 643, Barcelona 08028, Catalonia, Spain. EM rgirones@ub.edu RI Girones, Rosina/B-2975-2009; OI Girones, Rosina/0000-0002-1097-6395; Calvo LLorca, Miguel/0000-0002-4016-3336; Rodriguez Manzano, Jesus/0000-0002-2583-8366 FU Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, USA; 'Ministerio de Educacion y Ciencia' of the Spanish Government [AGL2008-05275-C03-01, AGL2011-30461-C02-01]; Humanitarian Innovations Fund (WADHE); European Commission Framework Program 7 [KBBE 213178] FX The research described in this manuscript was partially supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, USA and by grants from the 'Ministerio de Educacion y Ciencia' of the Spanish Government (grant numbers AGL2008-05275-C03-01, AGL2011-30461-C02-01), Humanitarian Innovations Fund (WADHE), and the European Commission Framework Program 7 project 'Integrated monitoring and control of foodborne viruses in European food supply chains (VITAL)' [grant number KBBE 213178] led by the coordination team of Nigel Cook (FERA, UK), Martin D'Agostino (FERA, UK) and Franco M. Ruggeri (ISS, Italy). Anna Carratala and Jesus Rodriguez-Manzano are fellows of the Spanish Ministry of Science. NR 23 TC 7 Z9 7 U1 1 U2 10 PU IWA PUBLISHING PI LONDON PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND SN 1477-8920 J9 J WATER HEALTH JI J. Water Health PY 2014 VL 12 IS 3 BP 436 EP 442 DI 10.2166/wh.2014.027 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Microbiology; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Microbiology; Water Resources GA AW2OT UT WOS:000346128700009 PM 25252347 ER PT S AU Ong, HL de Souza, LB Cheng, KT Ambudkar, IS AF Ong, Hwei Ling de Souza, Lorena B. Cheng, Kwong Tai Ambudkar, Indu S. BE Nilius, B Flockerzi, V TI Physiological Functions and Regulation of TRPC Channels SO MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL II SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE TRPC channels; Ca2+ signaling; Protein complex; Trafficking; Regulation; Function ID OPERATED CA2+ ENTRY; RECEPTOR POTENTIAL CHANNELS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; ACTIVATED CALCIUM-CHANNEL; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE LOCALIZATION; NONSELECTIVE CATION CHANNEL; PHOSPHOLIPASE-C-GAMMA; ANKYRIN-LIKE REPEAT; LIGHT-CHAIN KINASE AB The TRP-canonical (TRPC) subfamily, which consists of seven members (TRPC1-TRPC7), are Ca2+-permeable cation channels that are activated in response to receptor-mediated PIP2 hydrolysis via store-dependent and store-independent mechanisms. These channels are involved in a variety of physiological functions in different cell types and tissues. Of these, TRPC6 has been linked to a channelopathy resulting in human disease. Two key players of the store-dependent regulatory pathway, STIM1 and Orai1, interact with some TRPC channels to gate and regulate channel activity. The Ca2+ influx mediated by TRPC channels generates distinct intracellular Ca2+ signals that regulate downstream signaling events and consequent cell functions. This requires localization of TRPC channels in specific plasma membrane microdomains and precise regulation of channel function which is coordinated by various scaffolding, trafficking, and regulatory proteins. C1 [Ong, Hwei Ling; de Souza, Lorena B.; Cheng, Kwong Tai; Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov RI Brito de Souza, Lorena/N-3385-2014 OI Brito de Souza, Lorena/0000-0002-2462-6759 NR 177 TC 16 Z9 16 U1 0 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-319-05161-1; 978-3-319-05160-4 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2014 VL 223 BP 1005 EP 1034 DI 10.1007/978-3-319-05161-1_12 D2 10.1007/978-3-319-05161-1 PG 30 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA BB7UQ UT WOS:000346022900013 PM 24961978 ER PT S AU Choi, S Maleth, J Jha, A Lee, KP Kim, MS So, I Ahuja, M Muallem, S AF Choi, Seok Maleth, Jozsef Jha, Archana Lee, Kyu Pil Kim, Min Seuk So, Insuk Ahuja, Malini Muallem, Shmuel BE Nilius, B Flockerzi, V TI The TRPCs-STIM1-Orai Interaction SO MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL II SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE TRPC channels; STIM1; Gating; Physiology; Pathology ID OPERATED CA2+ ENTRY; STROMAL INTERACTION MOLECULE-1; ACTIVATED CALCIUM-CHANNEL; FAST CA2+-DEPENDENT INACTIVATION; PANCREATIC ACINAR-CELL; TRPC CHANNELS; PLASMA-MEMBRANE; CRAC CHANNELS; ORAI CHANNELS; INTRACEREBRAL HEMORRHAGE AB Ca2+ signaling entails receptor-stimulated Ca2+ release from the ER stores that serves as a signal to activate Ca2+ influx channels present at the plasma membrane, the store-operated Ca2+ channels (SOCs). The two known SOCs are the Orai and TRPC channels. The SOC-dependent Ca2+ influx mediates and sustains virtually all Ca2+-dependent regulatory functions. The signal that transmits the Ca2+ content of the ER stores to the plasma membrane is the ER resident, Ca2+-binding protein STIM1. STIM1 is a multidomain protein that clusters and dimerizes in response to Ca2+ store depletion leading to activation of Orai and TRPC channels. Activation of the Orais by STIM1 is obligatory for their function as SOCs, while TRPC channels can function as both STIM1-dependent and STIM1-independent channels. Here we discuss the different mechanisms by which STIM1 activates the Orai and TRPC channels, the emerging specific and non-overlapping physiological functions of Ca2+ influx mediated by the two channel types, and argue that the TRPC channels should be the preferred therapeutic target to control the toxic effect of excess Ca (2+) influx. C1 [Choi, Seok; Maleth, Jozsef; Jha, Archana; Ahuja, Malini; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Lee, Kyu Pil] Chungnam Natl Univ, Coll Vet Med, Dept Physiol, Taejon 305764, South Korea. [Kim, Min Seuk] Wonkwang Univ, Sch Dent, Dept Oral Physiol, Iksan, Jeonbuk, South Korea. [So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea. RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-112, Bethesda, MD 20892 USA. EM shmuel.muallem@nih.gov NR 103 TC 16 Z9 17 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-319-05161-1; 978-3-319-05160-4 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2014 VL 223 BP 1035 EP 1054 DI 10.1007/978-3-319-05161-1_13 D2 10.1007/978-3-319-05161-1 PG 20 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA BB7UQ UT WOS:000346022900014 PM 24961979 ER PT S AU Liao, YH Abramowitz, J Birnbaumer, L AF Liao, Yanhong Abramowitz, Joel Birnbaumer, Lutz BE Nilius, B Flockerzi, V TI The TRPC Family of TRP Channels: Roles Inferred (Mostly) from Knockout Mice and Relationship to ORAI Proteins SO MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL II SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE Ca2+ Influx; TRPC; ORAI; Icrac; SOCE; ROCE; TRPC physiology; TRPC pathophysiology; Knockout mice; Phenotype ID OPERATED CA2+ ENTRY; RECEPTOR POTENTIAL CHANNELS; PLASMA-MEMBRANE; VASCULAR MYOCYTES; STORE DEPLETION; TRPC1(-/-) MICE; CATION CHANNEL; CALCIUM INFLUX; ANGIOTENSIN-II; CRAC CHANNELS AB Aside from entering into cells through voltage gated Ca channels and Na/Ca exchangers in those cells that express these proteins, for all cells be they excitable or non-excitable, Ca2+ enters through channels that are activated downstream of phosphoinositide mobilization (activation of phospholipase C, PLC) and through channels that are activated secondary to depletion of internal stores. Depletion of internal stores activates plasma membrane channels known as ORAIs. Activation of PLCs activates the canonical class of transient receptor potential channels (TRPCs), and, because this activation also causes depletion of Ca2+ stores, also ORAI based channels. Whereas the activation of ORAI is a well-accepted phenomenon, it appears that TRPC channels also participate in Ca2+ entry triggered by store depletion with or without participation of ORAI molecules. Regardless of molecular makeup of TRPC containing channels, a plethora of studies have shown TRPCs to be important both in physiologic systems as well as in pathophysiologic phenomena. Particularly important in defining roles of TRPCs, have been studies with mice with targeted disruption of their genes, i.e., with TRPC KO mice. In this chapter we first focus on TRPCs as regulators of body functions in health and disease, and then focus on the possible make-up of the channels of which they participate. A hypothesis is set forth, whereby ORAI dimers are proposed to be regulatory subunits of tetrameric TRPC channels and serve as structural units that form ORAI channels either as dimers of dimers or trimers of dimers. C1 [Liao, Yanhong] Huazhong Univ Sci & Technol, Coll Med, Dept Anat, Wuhan 430074, Peoples R China. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liao, YH (reprint author), Huazhong Univ Sci & Technol, Coll Med, Dept Anat, Wuhan 430074, Peoples R China. EM yhliao1@gmail.com; abramow1@niehs.nih.gov; birnbau1@niehs.nih.gov RI Abramowitz, Joel/A-2620-2015 FU Intramural NIH HHS; NIEHS NIH HHS [Z01-ES-101684] NR 73 TC 11 Z9 11 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-319-05161-1; 978-3-319-05160-4 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2014 VL 223 BP 1055 EP 1075 DI 10.1007/978-3-319-05161-1_14 D2 10.1007/978-3-319-05161-1 PG 21 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA BB7UQ UT WOS:000346022900015 PM 24961980 ER PT J AU Niciu, MJ Mathews, DC Ionescu, DF Richards, EM Furey, ML Yuan, PX Nugent, AC Henter, ID Machado-Vieira, R Zarate, CA AF Niciu, Mark J. Mathews, Daniel C. Ionescu, Dawn F. Richards, Erica M. Furey, Maura L. Yuan, Peixiong Nugent, Allison C. Henter, Ioline D. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Biomarkers in mood disorders research: developing new and improved therapeutics SO REVISTA DE PSIQUIATRIA CLINICA LA English DT Editorial Material DE Biomarker; depression; bipolar disorder; anxiety; drug development ID INFLAMMATORY-BOWEL-DISEASE; D-ASPARTATE ANTAGONIST; ANTIDEPRESSANT RESPONSE; PSYCHIATRIC-DISORDERS; DRUG DEVELOPMENT; ALCOHOL DEPENDENCE; MENTAL-DISORDERS; SYSTEMS BIOLOGY; FAMILY-HISTORY; DEPRESSION AB Background: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. Objective: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. Methods: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors. Results: To date, early phase biomarker studies have sought to identify measures that can serve as "biosignatures", or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health's (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine's rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression. Discussion: These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics. C1 [Niciu, Mark J.; Mathews, Daniel C.; Ionescu, Dawn F.; Richards, Erica M.; Furey, Maura L.; Yuan, Peixiong; Nugent, Allison C.; Henter, Ioline D.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 10 Ctr Dr CRC,Unit 7 Southeast,Room 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu, Mark/0000-0002-5612-3021; Nugent, Allison/0000-0003-2569-2480 FU Intramural NIH HHS [Z99 MH999999] NR 41 TC 0 Z9 0 U1 0 U2 3 PU UNIV SAO PAULO, INST PSIQUIATRIA PI SAO PAULO PA RUA OVIDIO PIRES CAMPOS, 785, 1 ANDAR, SAO PAULO, 05403-010, BRAZIL SN 0101-6083 J9 REV PSIQ CLIN-BRAZIL JI Rev. Psiquiatr. Clin. PY 2014 VL 41 IS 5 BP 131 EP 134 DI 10.1590/0101-60830000000027 PG 4 WC Psychiatry SC Psychiatry GA AW1UU UT WOS:000346077100004 PM 26082563 ER PT S AU Osorio, AI Solis-Najera, SE Vazquez, F Wang, RL Tomasi, D Rodriguez, AO AF Osorio, A. I. Solis-Najera, S. E. Vazquez, F. Wang, R. L. Tomasi, D. Rodriguez, A. O. BE BernalAlvarado, JD GuzmanCabrera, R Brandan, ME TI Multi Circular-Cavity Surface Coil for Magnetic Resonance Imaging of Monkey's Brain at 4 Tesla SO XIII MEXICAN SYMPOSIUM ON MEDICAL PHYSICS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 13th Mexican Symposium on Medical Physics CY MAR 15-16, 2014 CL Univ Guanajuato, Campus Leon, Leon, MEXICO SP Mexican Phys Soc, Med Phys Div, Centro Latinoamericano Fisica, Inst Politecnico Nacl HO Univ Guanajuato, Campus Leon AB Animal models in medical research has been used to study humans diseases for several decades. The use of different imaging techniques together with different animal models offers a great advantage due to the possibility to study some human pathologies without the necessity of chirurgical intervention. The employ of magnetic resonance imaging for the acquisition of anatomical and functional images is an excellent tool because its noninvasive nature. Dedicated coils to perform magnetic resonance imaging experiments are obligatory due to the improvement on the signal-to-noise ratio and reduced specific absorption ratio. A specifically designed surface coil for magnetic resonance imaging of monkey's brain is proposed based on the multi circular-slot coil. Numerical simulations of the magnetic and electric fields were also performed using the Finite Integration Method to solve Maxwell's equations for this particular coil design and, to study the behavior of various vector magnetic field configurations and specific absorption ratio. Monkey's brain images were then acquired with a research-dedicated magnetic resonance imaging system at 4T, to evaluate the anatomical images with conventional imaging sequences. This coil showed good quality images of a monkey's brain and full compatibility with standard pulse sequences implemented in research-dedicated imager. C1 [Osorio, A. I.] Univ Autonoma Metropolitana Azcapotzalco, Dept Ciencias Basicas, Av San Pablo 180, Reynosa Tamaulipas 02200, Azcapotzalco, Mexico. [Solis-Najera, S. E.; Vazquez, F.] Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, DF, Mexico. [Wang, R. L.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Tomasi, D.] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD 20892 USA. [Rodriguez, A. O.] Univ Autonoma Metropolitana Iztapalapa, Dept Ingn Elect, Mexico City 09340, DF, Mexico. RP Osorio, AI (reprint author), Univ Autonoma Metropolitana Azcapotzalco, Dept Ciencias Basicas, Av San Pablo 180, Reynosa Tamaulipas 02200, Azcapotzalco, Mexico. EM solisnajera@ciencias.unam.mx RI Tomasi, Dardo/J-2127-2015 FU CONACYT [112092] FX S. E. S. wishes to thank the CONACYT for a posdoc stipend under grant no. 112092 NR 11 TC 0 Z9 0 U1 1 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1263-7 J9 AIP CONF PROC PY 2014 VL 1626 BP 159 EP 163 DI 10.1063/1.4901383 PG 5 WC Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Physics; Radiology, Nuclear Medicine & Medical Imaging GA BB7RK UT WOS:000345929100030 ER PT J AU Menke, A Casagrande, SS Cowie, CC AF Menke, Andy Casagrande, Sarah S. Cowie, Catherine C. TI The relationship of adiposity and mortality among people with diabetes in the US general population: a prospective cohort study SO BMJ OPEN LA English DT Article ID BODY-MASS INDEX; CARDIOVASCULAR RISK-FACTORS; ALL-CAUSE MORTALITY; OBESITY PARADOX; WAIST CIRCUMFERENCE; HEART-FAILURE; DISEASE; ADULTS; ASSOCIATION; OVERWEIGHT AB Objective: Several studies have found a U-shaped association between body mass index (BMI) and mortality in the general population. In similar studies among people with diabetes, the shape of the association is inconsistent. We investigated the relationship of BMI and waist circumference with mortality among people with diabetes. Setting: The Third National Health and Nutrition Examination Survey (NHANES III) and the 1999-2004 NHANES Mortality Studies were designed to be representative of the US general population. Baseline data were collected in 1988-2004. Participants: 2607 adults >= 20 years of age with diabetes. Primary Outcome Measure: Participants were followed through 31 December 2006 for mortality (n=668 deaths). Results: Compared with people with a BMI 18.5-24.9 kg/m(2), the HRs (95% CI) of mortality were 0.85 (0.60 to 1.21) for 25-29.9 kg/m(2), 0.87 (0.57 to 1.33) for 30-34.9 kg/m(2) and 1.05 (0.72 to 1.53) for >= 35 kg/m(2) after adjustment for age, sex, race-ethnicity, smoking status, education, income and diabetes duration. Compared with people in the lowest sex-specific quartile of waist circumference, the adjusted HRs (95% CI) of mortality were 1.03 (0.77 to 1.37) for the second quartile, 1.02 (0.73 to 1.42) for the third quartile and 1.12 (0.77 to 1.61) for the highest quartile of waist circumference. When modelled as a restricted quadratic spline with knots at the 10th, 50th and 90th centiles, BMI and waist circumference were not associated with mortality. Several sensitivity analyses were conducted and most found no significant association between measures of adiposity and mortality, but there were significant results suggesting a U-shaped association among people in the highest tertile of glycated haemoglobin (>= 7.1%), and there was an inverse association between BMI and mortality among people 20-44 years of age. Conclusions: In a nationally representative sample of the non-institutionalised US population with diabetes, BMI and waist circumference were not associated with risk of mortality. C1 [Menke, Andy; Casagrande, Sarah S.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Cowie, Catherine C.] NIDDKD, NIH, Bethesda, MD USA. RP Menke, A (reprint author), Social & Sci Syst Inc, Silver Spring, MD 20910 USA. EM amenke@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [GS10F0381L] FX This work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (GS10F0381L). NR 28 TC 5 Z9 5 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 11 AR e005671 DI 10.1136/bmjopen-2014-005671 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU7EA UT WOS:000345762300020 PM 25406156 ER PT J AU Karnati, HK Panigrahi, M Shaik, NA Greig, NH Bagadi, SAR Kamal, MA Kapalavayi, N AF Karnati, Hanuma K. Panigrahi, Manas Shaik, Noor A. Greig, Nigel H. Bagadi, S. Appala R. Kamal, Mohammad A. Kapalavayi, Nagaiah TI Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of beta-Catenin: Association with Human Glioma Progression SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Adheren junction; claudin 1 (CLDN1); claudin 5 (CLDN5); beta-catenin; glioma; Glioblastoma multiforme (GBM); tight junction (TJ) ID BLOOD-BRAIN-BARRIER; TIGHT JUNCTION PROTEINS; SYNDROMIC HEARING-LOSS; SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; MATRIX METALLOPROTEINASES; GLIOBLASTOMA-MULTIFORME; NEONATAL ICHTHYOSIS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS AB Glioblastoma multiforme is the most common form of intracranial malignancy in humans, and is characterized by aggressive tumor growth, tissue invasion and neurodegenerative properties. The present study investigated the expression status of tight junction associated Claudin 1 (CLDN1), Claudin 5 (CLDN5) and Adheren junction associated beta-catenin genes in the light of their critical role in the progression of both low- and high-grade human gliomas. Using quantitative PCR and Western blot methods the mRNA and protein status of CLDN1, CLDN5 and beta-catenin genes were studied in a total of 25 human gliomas of World Health Organization (WHO) grades I-IV, non-cancerous control brain tissues and their corresponding model cell lines (C6, U373, U118, T98 and U87MG). Quantitative analysis of the transcript and protein expression data showed that CLDN1 and CLDN5 were significantly down regulated (p=<0.001) in tumors of all four grades and model cell lines. This decrease in expression pattern was in accordance with the increasing grade of the tumor. A 4-fold stronger reduction of CLDN1 when compared to CLDN5 was evident in high-grade tumors. Interestingly, beta-catenin was up regulated in all tumor types we studied (p=<0.005). Our findings, suggest that down regulated CLDN1 and CLDN5 genes have potential relevance in relation to the progression of glioblastoma multiforme. Hence, their therapeutic targeting may provide both insight and leads to control the cellular proliferation and subsequent invasiveness among affected individuals. C1 [Karnati, Hanuma K.; Kapalavayi, Nagaiah] Gland Pharma Ltd, R&D, Dept Biotechnol, Hyderabad 500043, Andhra Pradesh, India. [Panigrahi, Manas] KIMS, Dept Neurosurg, Hyderabad 500003, Andhra Pradesh, India. [Shaik, Noor A.] King Abdulaziz Univ, Fac Med, Princess Al Jawhara Al Brahim Ctr Excellence Res, Dept Med Genet, Jeddah 21589, Saudi Arabia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Bagadi, S. Appala R.] ICMR, Natl Inst Pathol, Tumor Biol Lab, New Delhi 110029, India. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. RP Kapalavayi, N (reprint author), Gland Pharma Ltd Dundigal, Dept Biotechnol, Gandimaisamma X Roads, Hyderabad 500043, Andhra Pradesh, India. EM hanumabio@gmail.com; knagaiah@gmail.com RI shaik, noor/C-5509-2013 FU Gland Pharma Limited; KIMS, Hyderabad, India; National Institute of Pathology New Delhi, India; King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Intramural Research Program of the National Institute on Aging, Baltimore, MD, USA FX We thank Dr. Ashutosh Kumar, University of Hyderabad, for guiding us in real time PCR analysis, Dr. T. Prasad, University of Hyderabad, for Immunofluorescence images and Dr. Arun Kumar, Center for Finger Printing and Diagnostics (CDFD), Hyderabad, for manuscript input and corrections. We sincerely thank to Mr. Mohammad Hameed Khan, Krishna Institute of Medical Sciences (KIMS), Hyderabad, for help in obtaining fresh tissue samples. These studies were supported in part by Gland Pharma Limited (HKK, NK) and KIMS (MP), Hyderabad, India; by the National Institute of Pathology (SARB) New Delhi, India; by the King Abdulaziz University (NAS), Jeddah, Kingdom of Saudi Arabia; and by the Intramural Research Program of the National Institute on Aging (NHG), Baltimore, MD, USA. NR 86 TC 5 Z9 5 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 8 BP 1413 EP 1426 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AU6BE UT WOS:000345686300013 PM 25345514 ER PT J AU Mushtaq, G Greig, NH Khan, JA Kamal, MA AF Mushtaq, Gohar Greig, Nigel H. Khan, Jalaluddin A. Kamal, Mohammad A. TI Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Acetylcholinesterase; Alzheimer's disease; butyrylcholinesterase; cholinergic deficit; cholinesterase inhibitors; type 2 diabetes mellitus ID AMYLOID PRECURSOR PROTEIN; GRADE SYSTEMIC INFLAMMATION; ALPHA-LIPOIC ACID; SERUM BUTYRYLCHOLINESTERASE; BETA-PEPTIDE; K-VARIANT; SELECTIVE INHIBITORS; BRAIN ACETYLCHOLINE; CHOLINERGIC SYSTEM; MEMORY DYSFUNCTION AB Both Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) share the presence of systemic and neuro-inflammation, enhanced production and accumulation of beta-amyloid peptide and abnormal levels of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Altered levels of AChE and BuChE both in AD as well as in T2DM imply that those two enzymes may be playing a pivotal role in the pathogenesis of the two disorders. AD and T2DM are both characterized by elevated levels of AChE and BuChE in the plasma. On the other hand, in AD the brain levels of AChE go down while those of BuChE go up, resulting in deregulation in balance between AChE and BuChE. This imbalance and change in the AChE/BuChE ratio causes cholinergic deficit in the brain, i.e. deficiency in the brain neurotransmitter acetylcholine. With better understanding of the inter-relationship of AChE and BuChE levels in normality as well as abnormality, AD and T2DM can be effectively treated. Thus, general cholinesterase inhibitors that inhibit both AChE and BuChE as well as highly selective BuChE inhibitors may have potential therapeutic benefits in the treatment of AD and other related dementias. C1 [Mushtaq, Gohar; Khan, Jalaluddin A.] King Abdulaziz Univ, Coll Sci, Dept Biochem, Jeddah 21413, Saudi Arabia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. RP Mushtaq, G (reprint author), King Abdulaziz Univ, Coll Sci, Dept Biochem, Jeddah 21413, Saudi Arabia. EM gmushtaq2001@gmail.com RI Mushtaq, Gohar/G-5504-2015; Khan, Jalaluddin/O-4490-2016; OI Mushtaq, Gohar/0000-0003-4880-4035; Khan, Jalaluddin/0000-0003-2319-4023; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural NIH HHS NR 95 TC 8 Z9 9 U1 2 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 8 BP 1432 EP 1439 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AU6BE UT WOS:000345686300015 PM 25345511 ER PT J AU Reidy, M Masison, DC AF Reidy, Michael Masison, Daniel C. TI Yeast Prions Help Identify and Define Chaperone Interaction Networks SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Article DE Amyloid; chaperones; Hsp70; Hsp40; Hsp104; Hsp90; yeast prions ID HEAT-SHOCK PROTEINS; SACCHAROMYCES-CEREVISIAE PSI+; NUCLEOTIDE EXCHANGE FACTORS; BETA-SHEET STRUCTURE; HSP70 CHAPERONES; GUANIDINE-HYDROCHLORIDE; MOLECULAR CHAPERONES; HSP100 CHAPERONES; ANTAGONISTIC INTERACTIONS; AGGREGATED PROTEINS AB Proteins in the cell experience various stressful conditions that can affect their ability to attain and maintain the structural conformations they need to perform effectively. Protein chaperones are an important part of a cellular protein quality control system that protects the integrity of the proteome in the face of such challenges. Chaperones from different conserved families have multiple members that cooperate to regulate each other's activity and produce machines that perform a variety of tasks. The large numbers of related chaperones with both functionally overlapping and distinct activities allows fine-tuning of the machinery for specific tasks, but presents a daunting degree of complexity. Yeast prions are misfolded forms of cellular proteins whose propagation depends on the action of protein chaperones. Studying how propagation of yeast prions is affected by alterations in functions of various chaperones provides an approach to understanding this complexity. C1 [Reidy, Michael; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Reidy, M (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr, Bethesda, MD 20892 USA. EM reidym@mail.nih.gov NR 126 TC 2 Z9 2 U1 2 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 EI 1873-4316 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PY 2014 VL 15 IS 11 BP 1008 EP 1018 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AU6AF UT WOS:000345683800002 PM 25373385 ER PT J AU Djamshidian, A O'Sullivan, SS Tomassini, A Foltynie, T Limousin, P Aviles-Olmos, I Warner, TT Lees, AJ Averbeck, BB AF Djamshidian, Atbin O'Sullivan, Sean S. Tomassini, Alessandro Foltynie, Thomas Limousin, Patricia Aviles-Olmos, Iciar Warner, Thomas T. Lees, Andrew J. Averbeck, Bruno B. TI In a Rush to Decide: Deep Brain Stimulation and Dopamine Agonist Therapy in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Deep brain stimulation; dopamine agonists; Parkinson's disease; perceptual decision making ID SUBTHALAMIC NUCLEUS STIMULATION; DECISION-MAKING; IMPULSIVITY; BEHAVIORS; SALIENCE; REWARD AB Background: It has been suggested that all patients with Parkinson's disease (PD) who undergo functional neurosurgery have difficulties in slowing down in high conflict tasks. However, it is unclear whether concomitant dopaminergic medication is responsible for this impairment. Objective: To assess perceptual decision making in PD patients with bilateral deep brain stimulation. Methods: We tested 27 PD patients with bilateral deep brain stimulation on a task in which participants had to filter task relevant information from background noise. Thirteen patients were treated with Levodopa monotherapy and 14 patients were treated with Levodopa in combination with a dopamine agonist. Results were compared to healthy matched controls. Results: We found that all PD patients who were treated with a dopamine agonist made faster decisions than controls and PD patients who were not exposed to a dopamine agonist. Further, all patients made more errors than controls, but there was no difference between the two patient groups. Conclusions: Our results suggest that dopamine agonist therapy rather than deep brain stimulation is likely responsible for the inability to slow down in high conflict situations in PD. These results further strengthen the need to reduce dopamine agonists in PD patients undergoing functional neurosurgery in order to prevent them making inadvisable decisions. C1 [Djamshidian, Atbin; Warner, Thomas T.; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England. [Djamshidian, Atbin; Warner, Thomas T.; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England. [Djamshidian, Atbin] Univ Clin Innsbruck, Dept Neurol, Tyrol, Austria. [O'Sullivan, Sean S.] Natl Univ Ireland Univ Coll Cork, Cork Univ Hosp, Cork, Ireland. [Tomassini, Alessandro; Foltynie, Thomas; Limousin, Patricia; Aviles-Olmos, Iciar] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England. [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Djamshidian, A (reprint author), UCL, Reta Lila Weston Inst Neurol Studies, 1 Wakefield St, London WC1N 1PJ, England. EM a.djamshidian-tehrani@ucl.ac.uk RI Warner, Thomas/A-1454-2013 OI Warner, Thomas/0000-0001-6195-6995 FU Intramural NIH HHS [ZIA MH002928-04] NR 20 TC 5 Z9 5 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2014 VL 4 IS 4 BP 579 EP 583 DI 10.3233/JPD-140388 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AU8OL UT WOS:000345855800005 PM 25061059 ER PT J AU Cooper, DB Vanderploeg, RD Armistead-Jehle, P Lewis, JD Bowles, AO AF Cooper, Douglas B. Vanderploeg, Rodney D. Armistead-Jehle, Patrick Lewis, Jeffrey D. Bowles, Amy O. TI Factors associated with neurocognitive performance in OIF/OEF servicemembers with postconcussive complaints in postdeployment clinical settings SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE blast injuries; cognitive complaints; combat veterans; mild traumatic brain injury; neuropsychological assessment; OIF/OEF; performance validity; postconcussive symptoms; postdeployment; posttraumatic stress disorder ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHOLOGICAL STATUS RBANS; SYMPTOM VALIDITY TESTS; REPEATABLE BATTERY; PSYCHOMETRIC PROPERTIES; EVALUATION CONTEXT; OEF/OIF VETERANS; MILITARY SAMPLE; COMBAT VETERANS AB Cognitive difficulties are frequently reported by Operation Iraqi Freedom/Operation Enduring Freedom military personnel who sustained mild traumatic brain injuries (TBIs). The current study examined several potential factors that may contribute to self-reported cognitive difficulties in postdeployment clinical settings. Eighty-four subjects who sustained a mild or moderate TBI and reported cognitive difficulties underwent neurocognitive testing. Multiple regression analyses were used to determine the amount of variance in neurocognitive performance accounted for by the predictor variables (demographic, mechanism of injury, time since injury, headache severity, combat stress, postconcussive complaints, and effort/performance validity). The predictor variables collectively accounted for 51.7% of the variance in cognitive performance (F (8,72) = 11/99, p < 0.001). The most potent predictor of cognitive functioning was performance validity/effort, which uniquely accounted for 16.3% of the variance(p < 0.01). Self-reported symptom severity, including postconcussive complaints, combat stress, and headache intensity, accounted for 7.2% of the variance (p < 0.05). Demographic factors and injury characteristics, such as time since injury and mechanism of injury, were not significant predictive factors of cognitive performance. The findings of the current study underscore the need to include measurement of effort as part of neurocognitive evaluation in postdeployment settings when evaluating cognitive complaints associated with mild TBI. C1 [Cooper, Douglas B.; Vanderploeg, Rodney D.] Def & Vet Brain Injury Ctr, Silver Spring, MD USA. [Cooper, Douglas B.] San Antonio Mil Med Ctr, Dept Neurol, Ft Sam Houston, TX USA. [Vanderploeg, Rodney D.] James A Haley Vet Hosp, Tampa, FL 33612 USA. [Vanderploeg, Rodney D.] Univ S Florida, Dept Psychiat & Neurosci, Tampa, FL USA. [Vanderploeg, Rodney D.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Armistead-Jehle, Patrick] Munson Army Hlth Ctr, Concuss Clin, Ft Leavenworth, KS USA. [Lewis, Jeffrey D.] NINDS, Behav Neurol Unit, Bethesda, MD 20892 USA. [Bowles, Amy O.] San Antonio Mil Med Ctr, Traumat Brain Injury Serv, Dept Orthoped & Rehabil, Ft Sam Houston, TX USA. RP Cooper, DB (reprint author), MCHE MDU DVBIC, San Antonio Mil Med Ctr, Def & Vet Brain Injury Ctr, 3551 Roger Brooke Dr, Jbsa Ft Sam Houston, TX 78234 USA. EM douglas.b.cooper.ctr@mail.mil FU DVBIC through Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. FX This material was based on work supported in part by the DVBIC through contract support provided by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. NR 54 TC 3 Z9 3 U1 1 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 7 BP 1023 EP 1033 DI 10.1682/JRRD.2013.05.0104 PG 11 WC Rehabilitation SC Rehabilitation GA AU8JB UT WOS:000345841300002 PM 25479335 ER PT J AU Verma, M AF Verma, Mukesh TI Molecular profiling and companion diagnostics: where is personalized medicine in cancer heading? SO PERSONALIZED MEDICINE LA English DT Review DE biomarkers; cancer; companion diagnostics; epidemiology; epigenetics; genomics; omics technologies; outcome; personalized medicine; pharmacogenomics ID EPIGENOME-WIDE ASSOCIATION; CELL LUNG-CANCER; UNIQUE TUMOR PRINCIPLE; BREAST-CANCER; COLORECTAL-CANCER; METABOLOMICS APPROACH; COLON-CANCER; BIOMARKER DISCOVERY; METASTATIC MELANOMA; PRECISION MEDICINE AB The goal of personalized medicine is to use the right drug at the right dose - with minimal or no toxicity - for the right patient at the right time. Recent advances in understanding cell biology and pathways, and in using molecular 'omics' technologies to diagnose cancer, offer a strategic bridge to personalized medicine in cancer. Modern personalized medicine takes into account an individual's genetic makeup and disease history before developing a treatment regimen. The future of clinical oncology will be based on the use of predictive and prognostic biomarkers in patient management. Once implemented widely, personalized medicine will benefit patients and the healthcare system greatly. C1 NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20850 USA. RP Verma, M (reprint author), NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20850 USA. EM vermam@rnail.nih.gov NR 115 TC 1 Z9 1 U1 2 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PY 2014 VL 11 IS 8 BP 761 EP 771 DI 10.2217/PME.14.41 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU6XJ UT WOS:000345744400005 ER PT S AU Santosh, KC Candemir, S Jaeger, S Folio, L Karargyris, A Antani, S Thoma, G AF Santosh, K. C. Candemir, S. Jaeger, S. Folio, L. Karargyris, A. Antani, S. Thoma, G. GP IEEE TI Rotation Detection in Chest Radiographs based on Generalized Line Histogram of Rib-Orientations SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med DE Terms Chest radiographs; generalized line histogram; rib-orientations; rotation detection AB We present a generalized line histogram technique to compute global rib-orientation for detecting rotated lungs in chest radiographs. We use linear structuring elements, such as line seed filters, as kernels to convolve with edge images, and extract a set of lines from the posterior rib-cage. After convolving kernels in all possible orientations in the range [0, pi), we measure the angle for which the line histogram has maximum magnitude. This measure provides a good approximation of the global chest rib-orientation for each lung. A chest radiograph is said to be upright if the difference between the orientation angles of both lungs with respect to the horizontal axis, is negligible. We validate our method on sets of normal and abnormal images and argue that rib orientation can be used for rotation detection in chest radiographs as aid in quality control during image acquisition, and to discard images from training and testing data sets. In our test, we achieve a maximum accuracy of 90%. C1 [Santosh, K. C.; Candemir, S.; Jaeger, S.; Karargyris, A.; Antani, S.; Thoma, G.] NIH, Commun Engn Branch, US Natl Lib Med NLM, 8600 Rockville Pike, Bethesda, MD 20894 USA. [Folio, L.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Santosh, KC (reprint author), NIH, Commun Engn Branch, US Natl Lib Med NLM, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM santosh.kc@nih.gov; sema.candemir@nih.gov; stefan.jaeger@nih.gov; les.folio@nih.gov; alexandros.karargyris@nih.gov; sameer.antani@nih.gov; george.thoma@nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); National Library of Medicine (NLM); Lister Hill National Center for Biomedical Communications (LHNCBC) FX This research was supported [in part] by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and Lister Hill National Center for Biomedical Communications (LHNCBC). NR 17 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 138 EP 142 DI 10.1109/CBMS.2014.56 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200028 ER PT S AU Solomon, J Johnson, R Douglas, D Hammoud, D AF Solomon, Jeffrey Johnson, Reed Douglas, Deborah Hammoud, Dima GP IEEE TI New Image Analysis Technique for Quantitative Longitudinal Assessment of Lung Pathology on CT in Infected Rhesus Macaques SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med DE lung volume; image processing; histogram-based segmentation ID GROWTH; SEGMENTATION AB this paper describes a novel method of quantitative assessment of lung pathology derived from chest computed tomography (CT) scans in infected animal models, namely rhesus macaques. Tracking the extent of lung pathology is essential in the understanding of the natural history of infectious diseases and can be eventually used to predict prognosis and monitor response to preventative (vaccines) or therapeutic interventions. Our technique utilizes the histogram of voxel Hounsfield units (HU) within the segmented lung to track the percent change in "hyperdense volume" as a marker of disease over time. This method is not as susceptible to variability in lung inflation from breath hold techniques during the scanning process as are other techniques. Our quantitative lung pathology estimates using this technique correlated well with qualitative interpretation of lung pathology performed by a radiologist. C1 [Solomon, Jeffrey; Hammoud, Dima] NIH, Ctr Infect Dis Imaging, Ctr Clin, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. [Johnson, Reed] NIH, Natl Inst Allergy & Infect Dis, Emerging Viral Pathogens Sect, Bethesda, MD 20892 USA. [Douglas, Deborah] NIH, Natl Inst Allergy & Infect Dis, Integrated Res Facil, Bethesda, MD 20892 USA. RP Solomon, J (reprint author), NIH, Ctr Infect Dis Imaging, Ctr Clin, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM jsolomon@cc.nih.gov RI Hammoud, Dima/C-2286-2015 NR 7 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 169 EP 172 DI 10.1109/CBMS.2014.59 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200034 ER PT S AU Xue, ZY Antani, S Long, LR Demner-Fushman, D Thoma, GR AF Xue, Zhiyun Antani, Sameer Long, L. Rodney Demner-Fushman, Dina Thoma, George R. GP IEEE TI Body Segment Classification for Visible Human Cross Section Slices SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med DE Body segment classification; visible human data; body cross section ID RETRIEVAL; FEATURES AB Visible human data has been widely used in various medical research and computer science applications. We present a new application for this data: a method to classify which body segment a transverse cross section image belongs to. The labeling of the data is created with the guidance of an online body cross section tutorial. The visual properties of the images are represented using a variety of feature descriptors. To avoid problems that arise from the large dimensionality of features, feature selection is applied. The multi-class SVM is employed as the classifier. Both the CT scans and the color photographs of cryosections of the whole body (male and female) are used to test the proposed method. The high performance with overall accuracy above 98% on both the 2160 CT dataset and the 1870 cryosectional photos show the method is very promising. Because of its observed effectiveness on visible human data, we will extend our approach to classify figures in biomedical articles. C1 [Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Demner-Fushman, Dina; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Xue, ZY (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM xuez@mail.nih.gov; santani@mail.nih.gov; rlong@mail.nih.gov; gthoma@mail.nih.gov NR 21 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 199 EP 204 DI 10.1109/CBMS.2014.55 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200040 ER PT S AU Russ, DE Ho, KY Johnson, CA Friesen, MC AF Russ, Daniel E. Ho, Kwan-Yuet Johnson, Calvin A. Friesen, Melissa C. GP IEEE TI Computer-Based Coding of Occupation Codes for Epidemiological Analyses SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med DE Automated Coding; Occupational Coding AB Mapping job titles to standardized occupation classification (SOC) codes is an important step in evaluating changes in health risks over time as measured in inspection databases. However, manual SOC coding is cost prohibitive for very large studies. Computer based SOC coding systems can improve the efficiency of incorporating occupational risk factors into large-scale epidemiological studies. We present a novel method of mapping verbatim job titles to SOC codes using a large table of prior knowledge available in the public domain that included detailed description of the tasks and activities and their synonyms relevant to each SOC code. Job titles are compared to our knowledge base to find the closest matching SOC code. A soft Jaccard index is used to measure the similarity between a previously unseen job title and the knowledge base. Additional information such as standardized industrial codes can be incorporated to improve the SOC code determination by providing additional context to break ties in matches. C1 [Russ, Daniel E.; Ho, Kwan-Yuet; Johnson, Calvin A.] NIH, Ctr Informat Technol, Div Computat Biosci, Bldg 10, Bethesda, MD 20892 USA. [Friesen, Melissa C.] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Russ, DE (reprint author), NIH, Ctr Informat Technol, Div Computat Biosci, Bldg 10, Bethesda, MD 20892 USA. EM druss@mail.nih.gov; johnson@mail.nih.gov; friesenmc@mail.nih.gov RI Friesen, Melissa/A-5362-2009; OI Russ, Daniel/0000-0003-4040-4416 FU Intramural Research Programs of the Center for Information Technology and the National Cancer Institute FX This research was supported by the Intramural Research Programs of the Center for Information Technology and the National Cancer Institute. NR 10 TC 4 Z9 4 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 347 EP 350 DI 10.1109/CBMS.2014.79 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200068 ER PT S AU You, D Antani, S Demner-Fushman, D Thoma, GR AF You, Daekeun Antani, Sameer Demner-Fushman, Dina Thoma, George R. GP IEEE TI Does Figure-Text Improve Biomedical Article Retrieval? A Pilot Study SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med AB Graphical illustrations are often used in biomedical articles to convey statistical results, schematics, etc. They are frequently accompanied with superimposed text annotations, or figure-text. It is generally assumed that this figure-text provides information that complements associated textual metadata, such as the captions, or bibliographic citations for indexing the figures and enhanced retrieval quality. However, to the best of our knowledge nothing in the literature adequately supports the assumption of information gain. In this article, we report the results of a pilot study that compares image retrieval based on figure captions alone to that using figure-text in addition to captions. In the blind study two judges evaluated a set of figures retrieved on the topic of "lung cancer". We find that figure-text could help improve retrieval performance for specific queries. C1 [You, Daekeun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP You, D (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA. EM youd@mail.nih.gov; santani@mail.nih.gov; ddemner@mail.nih.gov; gthoma@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 471 EP 472 DI 10.1109/CBMS.2014.95 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200095 ER PT S AU You, D Antani, S Demner-Fushman, D Thoma, GR AF You, Daekeun Antani, Sameer Demner-Fushman, Dina Thoma, George R. GP IEEE TI A MRF Model for Biomedical Image Segmentation SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med AB We propose a Markov random field (MRF)-based method to segment photographic biomedical images into three image sub-regions, viz., tissue, photo, and background. Segmentation results are then used to extract local and global visual features to separate images with tissue, such as endoscopic images, from general photographs. C1 [You, Daekeun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. EM youd@mail.nih.gov; santani@mail.nih.gov; ddemner@mail.nih.gov; gthoma@mail.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 539 EP 540 DI 10.1109/CBMS.2014.128 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200128 ER PT J AU Anand, A Sharma, K Chen, W Sharma, NK AF Anand, Akshay Sharma, Kaushal Chen, Wei Sharma, Neel Kamal TI Using Current Data to Define New Approach in Age Related Macular Degeneration: Need to Accelerate Translational Research SO CURRENT GENOMICS LA English DT Article DE Age related macular degeneration; Mitochondrial genes; Epigenetics; SNP; Biomarkers; Translational research; Bio-informatics ID GENOME-WIDE ASSOCIATION; HIGH-DOSE SUPPLEMENTATION; COMPLEMENT FACTOR-H; MITOCHONDRIAL-DNA; CLINICAL-RESEARCH; VITAMIN-C; RETINAL DEGENERATION; FAMILIAL AGGREGATION; GEOGRAPHIC ATROPHY; MONOZYGOTIC TWINS AB Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease. C1 [Anand, Akshay; Sharma, Kaushal] Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India. [Chen, Wei] Univ Pittsburgh, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15224 USA. [Sharma, Neel Kamal] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD USA. RP Anand, A (reprint author), Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India. EM akshay1anand@rediffmail.com NR 89 TC 2 Z9 2 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 EI 1875-5488 J9 CURR GENOMICS JI Curr. Genomics PY 2014 VL 15 IS 4 BP 266 EP 277 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AT9CJ UT WOS:000345225300003 PM 25132797 ER PT J AU Wit, JM van Duyvenvoorde, HA van Klinken, JB Caliebe, J Bosch, CAJ Lui, JC Gijsbers, ACJ Bakker, E Breuning, MH Oostdijk, W Losekoot, M Baron, J Binder, G Ranke, MB Ruivenkamp, CAL AF Wit, Jan M. van Duyvenvoorde, Hermine A. van Klinken, Jan B. Caliebe, Janina Bosch, Cathy A. J. Lui, Julian C. Gijsbers, Antoinet C. J. Bakker, Egbert Breuning, Martijn H. Oostdijk, Wilma Losekoot, Monique Baron, Jeffrey Binder, Gerhard Ranke, Michael B. Ruivenkamp, Claudia A. L. TI Copy Number Variants in Short Children Born Small for Gestational Age SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Article DE Short stature; Small for gestational age; Growth; Copy number variations; Single nucleotide polymorphism array; Genetics ID IDIOPATHIC SHORT STATURE; BINDING GLOBULIN EXCESS; LERI-WEILL DYSCHONDROSTEOSIS; GENOME-WIDE ASSOCIATION; PAR1 DELETION; GENE AMPLIFICATION; CLINICAL-FEATURES; GROWTH-PLATE; REVEALS; IDENTIFICATION AB Background/Aims: In addition to genome-wide association studies (GWAS), height-associated genes may be uncovered by studying individuals with extreme short or tall stature. Methods: Genome-wide analysis for copy number variants (CNVs), using single nucleotide polymorphism (SNP) arrays, was performed in 49 index cases born small for gestational age with persistent short stature. Segregation analysis was performed, and genes in CNVs were compared with information from GWAS, gene expression in rodents' growth plates, and published information. Results: CNVs were detected in 13 cases. In 5 children a known cause of short stature was found: UPD7, UPD14, a duplication of the SHOX enhancer region, an IGF1R deletion, and a 22q11.21 deletion. In the remaining 8 cases, potential pathogenic CNVs were detected, either de novo (n = 1), segregating (n = 2), or not segregating with short stature (n = 5). Bioinformatic analysis of the de novo and segregating CNVs suggested that HOXD4, AGPS, PDE11A, OSBPL6, PRKRA and PLEKHA3, and possibly DGKB and TNFRSF11B are potential candidate genes. A SERPINA7 or NRK defect may be associated with an X-linked form of short stature. Conclusion: SNP arrays detected 5 known causes of short stature with prenatal onset and suggested several potential candidate genes. (C) 2014 S. Karger AG, Basel C1 [Wit, Jan M.; Oostdijk, Wilma] Leiden Univ, Dept Pediat, Med Ctr, NL-2300 RC Leiden, Netherlands. [van Duyvenvoorde, Hermine A.; Bosch, Cathy A. J.; Gijsbers, Antoinet C. J.; Bakker, Egbert; Breuning, Martijn H.; Losekoot, Monique; Ruivenkamp, Claudia A. L.] Leiden Univ, Dept Clin Genet, Med Ctr, NL-2300 RC Leiden, Netherlands. [van Klinken, Jan B.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RC Leiden, Netherlands. [Caliebe, Janina; Binder, Gerhard; Ranke, Michael B.] Univ Tubingen, Childrens Hosp, Paediat Endocrinol Sect, Tubingen, Germany. [Lui, Julian C.; Baron, Jeffrey] NIH, Sect Growth & Dev, Bethesda, MD 20892 USA. RP Wit, JM (reprint author), Leiden Univ, Dept Pediat, Med Ctr, S6-P,POB 9600, NL-2300 RC Leiden, Netherlands. EM j.m.wit@lumc.nl FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH FX We are grateful to Pfizer for an unrestricted grant for carrying out the SNP arrays, to the patients and their parents for participating in this study, and to the physicians for referring the patients. Special thanks go to Linda Johnston-Rohrbasser and Linda Fryklund of the NESTEGG Consortium. The contributions of J.C.L. and J.B. were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH. NR 60 TC 7 Z9 9 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2014 VL 82 IS 5 BP 310 EP 318 DI 10.1159/000367712 PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA AU2LM UT WOS:000345449800004 PM 25300501 ER PT J AU Jochmanova, I Zelinka, T Widimsky, J Pacak, K AF Jochmanova, I. Zelinka, T. Widimsky, J., Jr. Pacak, K. TI HIF Signaling Pathway in Pheochromocytoma and Other Neuroendocrine Tumors SO PHYSIOLOGICAL RESEARCH LA English DT Review DE Pheochromocytoma; Paraganglioma; Hypoxia-inducible factor; Oxygen sensing; Therapy ID HYPOXIA-INDUCIBLE-FACTOR; POLYCYTHEMIA-PARAGANGLIOMA SYNDROME; RENAL-CELL CARCINOMA; GERMLINE MUTATIONS; SPORADIC PHEOCHROMOCYTOMAS; TRANSCRIPTION FACTOR; SOMATIC MUTATIONS; MAMMALIAN TARGET; GENE-EXPRESSION; RAPAMYCIN MTOR AB Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic-or parasympathetic-derived chromaffin tissue. To date, eighteen PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIF alpha signaling has also been shown to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors. C1 [Jochmanova, I.] Safarik Univ, Fac Med, Dept Internal Med 1, Kosice, Slovakia. [Jochmanova, I.; Pacak, K.] Eunice Kennedy Shriver NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Zelinka, T.; Widimsky, J., Jr.] Charles Univ Prague, Fac Med 1, Dept Endocrinol & Metab, Dept Med 3, Prague, Czech Republic. [Zelinka, T.; Widimsky, J., Jr.] Gen Univ Hosp, Prague, Czech Republic. RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Program Reprod & Adult Endocrinol, Sect Med Neuroendocrinol, NIH, Bldg 10-CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Jochmanova, Ivana/I-9011-2016; Zelinka, Tomas/D-4276-2017 OI Jochmanova, Ivana/0000-0003-2346-461X; Zelinka, Tomas/0000-0003-3395-8373 FU RVO-VFN [64165]; Intramural Research Program of the National Institutes of Health, NICHD FX Supported by RVO-VFN 64165 and by the Intramural Research Program of the National Institutes of Health, NICHD. NR 93 TC 12 Z9 12 U1 0 U2 12 PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PI PRAGUE 4 PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC SN 0862-8408 EI 1802-9973 J9 PHYSIOL RES JI Physiol. Res. PY 2014 VL 63 SU 2 BP S251 EP S262 PG 12 WC Physiology SC Physiology GA AU4OH UT WOS:000345590400002 PM 24908231 ER PT J AU Gavrielides, MA Conway, C O'Flaherty, N Gallas, BD Hewitt, SM AF Gavrielides, Marios A. Conway, Catherine O'Flaherty, Neil Gallas, Brandon D. Hewitt, Stephen M. TI Observer Performance in the Use of Digital and Optical Microscopy for the Interpretation of Tissue-Based Biomarkers SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID CELLULAR IMAGING-SYSTEM; IN-SITU HYBRIDIZATION; BREAST-CANCER; VIRTUAL MICROSCOPY; SURGICAL PATHOLOGY; QUANTITATIVE IMMUNOHISTOCHEMISTRY; MULTISITE PERFORMANCE; HER2/NEU EXPRESSION; PROTEIN EXPRESSION; HER-2/NEU STATUS AB Background. We conducted a validation study of digital pathology for the quantitative assessment of tissue-based biomarkers with immunohistochemistry. Objective. To examine observer agreement as a function of viewing modality (digital versus optical microscopy), whole slide versus tissue microarray (TMA) review, biomarker type (HER2 incorporating membranous staining and Ki-67 with nuclear staining), and data type (continuous and categorical). Methods. Eight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97 cores), using digital and optical microscopy. Results. Results showed relatively high overall interobserver and intermodality agreement, with different patterns specific to biomarker type. For HER2, there was better interobserver agreement for optical compared to digital microscopy for whole slides as well as better interobserver and intermodality agreement for TMAs. For Ki-67, those patterns were not observed. Conclusions. The differences in agreement patterns when examining different biomarkers and different scoring methods and reviewing whole slides compared to TMA stress the need for validation studies focused on specific pathology tasks to eliminate sources of variability that might dilute findings. The statistical uncertainty observed in our analyses calls for adequate sampling for each individual task rather than pooling cases. C1 [Gavrielides, Marios A.; O'Flaherty, Neil; Gallas, Brandon D.] US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Conway, Catherine; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Conway, Catherine] Leica Biosyst, Vista, CA 92081 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Food and Drug Administration's Office of Women's Health (OWH) FX The authors are grateful for the pathologists who participated in this study: Meghna Alimchandani, M. D., David Kleiner, M. D., Ph.D., Alina Nicolae, M. D., Tan Ngyuen, M. D., Stephen Hewitt M. D., Ph.D., Gregory Riedlinger, M. D., Ph.D., Jackie Wieneke, M. D., and Avi Rosenberg, M. D., Ph.D. The study would not be possible without their time and effort. The authors would also like to thank Wei-Chung Cheng, Ph.D., and Hugo Caseres for their assistance and expertise regarding monitor color calibration. This work was supported by the Food and Drug Administration's Office of Women's Health (OWH) through a research grant to Marios Gavrielides and Nicholas Petrick. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 54 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2210-7177 EI 2210-7185 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2014 AR 157308 DI 10.1155/2014/157308 PG 10 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AU1ZW UT WOS:000345416900001 ER PT J AU Fargo, JH Rochowski, A Giri, N Savage, SA Olson, SB Alter, BP AF Fargo, John H. Rochowski, Andrzej Giri, Neelam Savage, Sharon A. Olson, Susan B. Alter, Blanche P. TI Comparison of Chromosome Breakage in Non-Mosaic and Mosaic Patients with Fanconi Anemia, Relatives, and Patients with Other Inherited Bone Marrow Failure Syndromes SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE Chromosome breakage; Diepoxybutane; Fanconi anemia; Inherited bone marrow failure; Mitomycin C ID NATURAL GENE-THERAPY; SOMATIC MOSAICISM; NITROGEN-MUSTARD; DIAGNOSIS; CANCER; SUSCEPTIBILITY; MUTATIONS; AGENTS AB Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome (IBMFS). Affected individuals must be distinguished from relatives, patients with mosaicism must be identified, and patients with other IBMFS classified as non-FA. The diagnostic feature of FA is increased chromosomal breakage in blood lymphocytes cultured with diepoxybutane or mitomycin C. Here, we sought a method to uniquely identify patients with FA with mosaicism, using cells from participants in the National Cancer Institute IBMFS cohort. Lymphocytes were treated with diepoxybutane or mitomycin C, and metaphases scored for breaks and radials. Analyses included the percentage of cells with any aberration, breaks per cell, and breaks per aberrant cell. There were 26 patients with FA (4 mosaics), 46 FA relatives, and 62 patients with a non-FA IBMFS. By all analytic methods, patients with FA were abnormal compared with other groups. Those with FA mosaicism had more breakage than relatives or patients with non-FA IBMFS, but there was some individual overlap. The choices of clastogen are laboratory-dependent, but there was no method or analysis of lymphocytes that clearly distinguished all individuals mosaic for FA from relatives or patients with other IBMFS. Thus, genotyping remains the best method for providing absolute clarity. (C) 2014 S. Karger AG, Basel. C1 [Fargo, John H.; Giri, Neelam; Savage, Sharon A.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20850 USA. [Fargo, John H.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Olson, Susan B.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Rochowski, Andrzej] Queensway Carleton Hosp, Ottawa, ON, Canada. RP Alter, BP (reprint author), NCI, Div Canc Epidemiol & Genet DCEG, 9609 Med Ctr Dr,Room 6E452, Rockville, MD 20850 USA. EM alterb@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural Program of the National Institutes of Health; National Cancer Institute [N02-CP-11019, N02-CP-65504, N02-CP-65501]; National Institutes of Health, Heart, Lung, and Blood Institute [NIH/NHLBI 5 P01 HL048546] FX We are grateful to all the patients who participate in the National Cancer Institute IBMFS cohort, to the physicians who referred the patients, and to our colleagues in the Clinical Genetics Branch of the National Cancer Institute and the subspecialty clinics at the National Institutes of Health for their evaluations of the patients. We thank Lisa Leathwood, RN; Ann Carr, MS, CGC; Maureen Risch, RN and the other members of the IBMFS team at Westat, Inc. for their extensive efforts. This work was supported in part by the Intramural Program of the National Institutes of Health and the National Cancer Institute and by contracts N02-CP-11019, N02-CP-65504, and N02-CP-65501 as well as by a grant from the National Institutes of Health, Heart, Lung, and Blood Institute (NIH/NHLBI 5 P01 HL048546) to S.B.O. NR 28 TC 5 Z9 5 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2014 VL 144 IS 1 BP 15 EP 27 DI 10.1159/000366251 PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA AT6XS UT WOS:000345080800003 PM 25227706 ER PT J AU Craigie, R AF Craigie, Robert TI The road to HIV-1 integrase inhibitors: the case for supporting basic research SO FUTURE VIROLOGY LA English DT Article DE AIDS; basic science; HIV-1; integrase inhibitors ID ROUS-SARCOMA-VIRUS; DEPENDENT DNA-POLYMERASE; STRAND TRANSFER; RETROVIRAL INTEGRATION; VIRAL-DNA; IN-VITRO; PROTEIN; PATIENT; CELLS; TRANSPOSITION AB AIDS has been transformed from a death sentence to a manageable disease for many patients with access to combination antiviral therapy. It is informative to look back on some of the key advances that have led to this transformation. The arsenal of tools currently available to clinicians now includes inhibitors of the viral reverse transcriptase, protease and integrase enzymes. The author discusses some of the key advances that have led to this transformation with an emphasis on the role of basic science in developing integrase inhibitors. Many of the stepping-stones could not easily have been foreseen to lead to medical advances. Treatments for diseases that are yet to emerge will likely depend on the progress made in basic science today. C1 Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov FU Intramural Program of NIDDK; NIH; AIDS Targeted Antiviral Program of the Office of the Director of the NIH FX This work was supported by the Intramural Program of NIDDK, the NIH and the AIDS Targeted Antiviral Program of the Office of the Director of the NIH. We thank Alan Engelman for comments on the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 29 TC 0 Z9 0 U1 2 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PY 2014 VL 9 IS 10 BP 899 EP 903 DI 10.2217/FVL.14.77 PG 5 WC Virology SC Virology GA AU0BA UT WOS:000345286900005 PM 25431615 ER PT S AU Raghavachari, N AF Raghavachari, Nalini BE Bunting, KD Qu, CK TI Gene Expression Profiling of Hematopoietic Stem Cells (HSCs) SO HEMATOPOIETIC STEM CELL PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HSC; mRNA; Gene expression profiling; Transcriptome; Microarrays; Next-generation sequencing; RNA-seq ID RNA-SEQ; REGENERATIVE MEDICINE; CORD BLOOD; TRANSCRIPTOME; THERAPIES; SUBSETS; ENGRAFTMENT; RECEPTOR; DISEASE AB Transcriptomic analysis to decipher the molecular phenotype of hematopoietic stem cells, regulatory mechanisms directing their life cycle, and the molecular signals mediating proliferation, mobilization, migration, and differentiation is believed to unravel disease-specific disturbances in hematological diseases and assist in the development of novel cell-based clinical therapies in this era of genomic medicine. The recent advent in genomic tools and technologies is now enabling the study of such comprehensive transcriptional characterization of cell types in a robust and successful manner. This chapter describes detailed protocols for isolating RNA from purified population of hematopoietic cells and gene expression profiling of those purified cells using both microarrays (Affymetrix) and RNA-Seq technology (Illumina Platform). C1 NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. RP Raghavachari, N (reprint author), NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 42 TC 0 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1133-2; 978-1-4939-1132-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1185 BP 91 EP 119 DI 10.1007/978-1-4939-1133-2_7 D2 10.1007/978-1-4939-1133-2 PG 29 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB6RC UT WOS:000344939500008 PM 25062624 ER PT J AU Wang, L Di, LJ Noguchi, CT AF Wang, Li Di, Lijun Noguchi, Constance Tom TI Erythropoietin, a Novel Versatile Player Regulating Energy Metabolism beyond the Erythroid System SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Erythropoietin; pleiotropic cytokine; erythroid system ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACTIVATED PROTEIN-KINASE; DIET-INDUCED OBESITY; ISCHEMIA-REPERFUSION INJURY; PANCREATIC BETA-CELLS; PLACEBO-CONTROLLED TRIAL; FOCAL CEREBRAL-ISCHEMIA; HUMAN ENDOTHELIAL-CELLS; HUMAN SKELETAL-MUSCLE; FATTY-ACID OXIDATION AB Erythropoietin (EPO), the required cytokine for promoting the proliferation and differentiation of erythroid cells to stimulate erythropoiesis, has been reported to act as a pleiotropic cytokine beyond hematopoietic system. The various activities of EPO are determined by the widespread distribution of its cell surface EPO receptor (EpoR) in multiple tissues including endothelial, neural, myoblasts, adipocytes and other cell types. EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed. The investigations of EPO activity in animals and the expression analysis of EpoR provide more insights on the potential of EPO in regulating energy metabolism and homeostasis. The findings of crosstalk between EPO and some important energy sensors and the regulation of EPO in the cellular respiration and mitochondrial function further provide molecular mechanisms for EPO activity in metabolic activity regulation. In this review, we will summarize the roles of EPO in energy metabolism regulation and the activity of EPO in tissues that are tightly associated with energy metabolism. We will also discuss the effects of EPO in regulating oxidative metabolism and mitochondrial function, the interactions between EPO and important energy regulation factors, and the protective role of EPO from stresses that are related to metabolism, providing a brief overview of previously less appreciated EPO biological function in energy metabolism and homeostasis. C1 [Wang, Li; Di, Lijun] Univ Macau, Fac Hlth Sci, Macau, Peoples R China. [Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Wang, L (reprint author), Univ Macau, Fac Hlth Sci, Macau, Peoples R China. EM liwang@umac.mo; lijundi@umac.mo NR 233 TC 25 Z9 27 U1 0 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2014 VL 10 IS 8 BP 921 EP 939 DI 10.7150/ijbs.9518 PG 19 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AT4AZ UT WOS:000344881300011 PM 25170305 ER PT J AU Budhu, A Terunuma, A Zhang, G Hussain, SP Ambs, S Wang, XW AF Budhu, Anuradha Terunuma, Atsushi Zhang, Geng Hussain, S. Perwez Ambs, Stefan Wang, Xin Wei TI Metabolic Profiles are Principally Different between Cancers of the Liver, Pancreas and Breast SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Breast; Cancer; Liver; Metabolite; Pancreas ID UNKNOWN PRIMARY SITE; HEPATOCELLULAR-CARCINOMA; EXPRESSION SIGNATURE; PROGRESSION; PREDICTION; PROGNOSIS; IDENTIFY; TUMORS AB Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin. C1 [Budhu, Anuradha; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Terunuma, Atsushi; Ambs, Stefan] NCI, Mol Epidemiol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhang, Geng; Hussain, S. Perwez] NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Budhu, A (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3050A, Bethesda, MD 20892 USA. EM budhua@mail.nih.gov RI Wang, Xin/B-6162-2009 FU Intramural Research Program of the Center for Cancer Research; US National Cancer Institute; NCI Director's Innovation Awards FX We thank Karen Yarrick for bibliographic assistance. This work was supported by the Intramural Research Program of the Center for Cancer Research, the US National Cancer Institute and NCI Director's Innovation Awards to Stefan Ambs and Anuradha Budhu. NR 21 TC 4 Z9 4 U1 1 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2014 VL 10 IS 9 BP 966 EP 972 DI 10.7150/ijbs.9810 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AT9FG UT WOS:000345232700003 PM 25210494 ER PT J AU Klar, AJS AF Klar, Amar J. S. TI Selective Chromatid Segregation Mechanism Invoked For the Human Congenital Mirror Hand Movement Disorder Development by RAD51 Mutations: A Hypothesis SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Mirror hand movement disorder; Selective chromatid segregation mechanism; Brain laterality development; rad51 mutation etiology; Asymmetric cell division mechanism ID FISSION YEAST; EPIGENETIC STATES; CELL-DIVISION; DNA STRANDS; DCC; ASYMMETRY; REPLICATION; MEIOSIS; MITOSIS; MODEL AB The vertebrate body plan externally is largely symmetrical across the midline but internal organs develop asymmetrically. The biological basis of asymmetric organ development has been investigated extensively for years, although the proposed mechanisms remain controversial. By comparison, the biological origin of external organs symmetry has not been extensively investigated. Bimanual hand control is one such external organs symmetry allowing independent motor control movements of both hands to a person. This gap in our knowledge is illustrated by the recent reports of heterozygous rad51 mutations causing mysterious symptoms of congenital mirror hand movement disorder (MM) in humans with 50% penetrance by an unknown mechanism. The analysis of mutations that vary symmetry or asymmetry could be exploited to decipher the mechanisms of laterality development. Here I present a hypothesis for explaining 50% penetrance of the rad51 mutation. The MM's origin is explained with the Somatic Strand-specific Imprinting and selective sister chromatid Segregation (SSIS) hypothesis proposed originally as the mechanism of asymmetric cell division to promote visceral organs body plan laterality development in vertebrates. By hypothesis, random sister chromatid segregation in mitosis occurs for a specific chromosome due to rad51/RAD51 constitution causing MM disorder development in 50% of subjects. C1 NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM klara@mail.nih.gov FU National Cancer Institute, National Institutes of Health FX I thank my colleagues Donald Court and Sharon Moore and Mark Johnston (University of Colorado, Denver) for editorial suggestions on the manuscript. The Intramural Research Program of the National Cancer Institute, National Institutes of Health, supports this research. NR 28 TC 2 Z9 2 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2014 VL 10 IS 9 BP 1018 EP 1023 DI 10.7150/ijbs.9886 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AT9FG UT WOS:000345232700009 PM 25210500 ER PT J AU Scheuing, L Chiu, CT Liao, HM Linares, GR Chuang, DM AF Scheuing, Lisa Chiu, Chi-Tso Liao, Hsiao-Mei Linares, Gabriel R. Chuang, De-Maw TI Preclinical and Clinical Investigations of Mood Stabilizers for Huntington's Disease: What Have We Learned? SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Huntington's disease; Lithium; Glycogen Synthase Kinase-3 Inhibitor; Valproic Acid; Histone Deacetylase Inhibitor; Therapeutic Potential ID GLYCOGEN-SYNTHASE KINASE-3-BETA; RECEPTOR-MEDIATED EXCITOTOXICITY; HISTONE DEACETYLASE INHIBITORS; CEREBRAL CORTICAL-NEURONS; INCLUSION-BODY FORMATION; CREB-BINDING PROTEIN; REDUCES BRAIN-DAMAGE; KAPPA-B ACTIVATION; HEAT-SHOCK-PROTEIN; DOUBLE-BLIND TRIAL AB Huntington's disease (HD) is a lethal, autosomal dominant neurodegenerative disorder caused by CAG repeat expansions at exon 1 of the huntingtin (Htt) gene, which encodes for a mutant huntingtin protein (mHtt). Prominent symptoms of HD include motor dysfunction, characterized by chorea; psychiatric disturbances such as mood and personality changes; and cognitive decline that may lead to dementia. Pathologically multiple complex processes and pathways are involved in the development of HD, including selective loss of neurons in the striatum and cortex, dysregulation of cellular autophagy, mitochondrial dysfunction, decreased neurotrophic and growth factor levels, and aberrant regulation of gene expression and epigenetic patterns. No cure for HD presently exists, nor are there drugs that can halt the progression of this devastating disease. Therefore, the need to discover neuroprotective modalities to combat HD is critical. In basic and preclinical studies using cellular and animal HD models, the mood stabilizers lithium and valproic acid (VPA) have shown multiple beneficial effects, including behavioral and motor improvement, enhanced neuroprotection, and lifespan extension. Recent studies in transgenic HD mice support the notion that combined lithium/VPA treatment is more effective than treatment with either drug alone. In humans, several clinical studies of HD patients found that lithium treatment improved mood, and that VPA treatment both stabilized mood and moderately reduced chorea. In contrast, other studies observed that the hallmark features of HD were unaffected by treatment with either lithium or VPA. The current review discusses preclinical and clinical investigations of the beneficial effects of lithium and VPA on HD pathophysiology. C1 [Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Linares, Gabriel R.; Chuang, De-Maw] Natl Inst Mental Hlth, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), Natl Inst Mental Hlth, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). The authors thank Ioline Henter and Peter Leeds of the NIMH, NIH for their excellent editorial assistance. NR 170 TC 15 Z9 15 U1 1 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2014 VL 10 IS 9 BP 1024 EP 1038 DI 10.7150/ijbs.9898 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AT9FG UT WOS:000345232700010 PM 25285035 ER PT J AU Lee, SW Jang, S Pyakuryal, AP Chang, K Sioa, TT AF Lee, Sung-Woo Jang, Sunyoung Pyakuryal, Anil P. Chang, Kenneth Sioa, Terence T. TI The impact of CyberKnife's prescription isodose percentage on intracranial target planning SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Letter ID GAMMA-KNIFE RADIOSURGERY; STEREOTACTIC RADIOSURGERY; BRAIN METASTASES; EQUIVALENCE C1 [Lee, Sung-Woo] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Lee, Sung-Woo] Rhode Isl Hosp, Dept Radiat Oncol, Providence, RI USA. [Jang, Sunyoung] Princeton Radiat Oncol, Jamesburg, NJ USA. [Pyakuryal, Anil P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chang, Kenneth; Sioa, Terence T.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. RP Lee, SW (reprint author), Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. EM terencesio@gmail.com NR 8 TC 1 Z9 1 U1 1 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2014 VL 15 IS 5 BP 278 EP 280 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT7MQ UT WOS:000345121900026 ER PT J AU Yan, T Mizutani, A Chen, L Takaki, M Hiramoto, Y Matsuda, S Shigehiro, T Kasai, T Kudoh, T Murakami, H Masuda, J Hendrix, MJC Strizzi, L Salomon, DS Fu, L Seno, M AF Yan, Ting Mizutani, Akifumi Chen, Ling Takaki, Mai Hiramoto, Yuki Matsuda, Shuichi Shigehiro, Tsukasa Kasai, Tomonari Kudoh, Takayuki Murakami, Hiroshi Masuda, Junko Hendrix, Mary J. C. Strizzi, Luigi Salomon, David S. Fu, Li Seno, Masaharu TI Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles SO JOURNAL OF CANCER LA English DT Article DE cancer stem cells; mouse induced pluripotent stem cells; extracellular vesicles; cancerous niche; liposarcoma ID EPITHELIAL-MESENCHYMAL TRANSITION; LUNG-CANCER; TRANSCRIPTIONAL REGULATION; INITIATING CELLS; PROGENITOR CELLS; SELF-RENEWAL; DIFFERENTIATION; MICROVESICLES; EXPRESSION; GLIOBLASTOMA AB Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors. C1 [Yan, Ting; Mizutani, Akifumi; Takaki, Mai; Hiramoto, Yuki; Matsuda, Shuichi; Shigehiro, Tsukasa; Kasai, Tomonari; Kudoh, Takayuki; Murakami, Hiroshi; Masuda, Junko; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Biotechnol, Kita Ku, Okayama 7008530, Japan. [Mizutani, Akifumi] Tianjin Cent Hosp Gynecol Obstet, Dept Pathol, Tianjin 300100, Peoples R China. [Hendrix, Mary J. C.; Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Lurie Childrens Res Ctr, Chicago, IL 60614 USA. [Salomon, David S.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Fu, Li] Tianjin Med Univ, Canc Hosp, Dept Breast Canc Pathol & Res Lab, State Key Lab Breast Canc Res, Tianjin, Peoples R China. RP Mizutani, A (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Biotechnol, Kita Ku, 3-1-1 Tsushima Naka, Okayama 7008530, Japan. EM mizut-a@okayama-u.ac.jp; mseno@okayama-u.ac.jp RI SENO, Masaharu /B-2092-2011 OI SENO, Masaharu /0000-0001-8547-6259 FU Japan Society for Promotion of Science (JSPS) [23650598, 24501315] FX This research has been performed under the Grant-in-Aid for Challenging Exploratory Research No. 23650598 (M. S.) and the Grant-in-Aid for Scientific Research (C) No. 24501315 (A. M.), Japan Society for Promotion of Science (JSPS). NR 52 TC 7 Z9 7 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2014 VL 5 IS 7 BP 572 EP 584 DI 10.7150/jca.8865 PG 13 WC Oncology SC Oncology GA AT8ZI UT WOS:000345217100008 PM 25057308 ER PT J AU Kasukurti, A Eggleton, CD Desai, SA Disharoon, DI Marr, DWM AF Kasukurti, A. Eggleton, C. D. Desai, S. A. Disharoon, D. I. Marr, D. W. M. TI A simple microfluidic dispenser for single-microparticle and cell samples SO LAB ON A CHIP LA English DT Article ID FLOW-CYTOMETRY; DEVICES; SORTER; BACTERIA; DILUTION; BIOLOGY; SYSTEMS; TOOLS AB Non-destructive isolation of single-cells has become an important need for many biology research laboratories; however, there is a lack of easily employed and inexpensive tools. Here, we present a single-particle sample delivery approach fabricated from simple, economical components that may address this need. In this, we employ unique flow and timing strategies to bridge the significant force and length scale differences inherent in transitioning from single particle isolation to delivery. Demonstrating this approach, we use an optical trap to isolate individual microparticles and red blood cells that are dispensed within separate 50 mu l droplets off a microfluidic chip for collection into microscope slides or microtiter plates. C1 [Kasukurti, A.; Disharoon, D. I.; Marr, D. W. M.] Colorado Sch Mines, Golden, CO 80401 USA. [Eggleton, C. D.] Univ Maryland, Dept Mech Engn, Baltimore, MD 21201 USA. [Desai, S. A.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Marr, DWM (reprint author), Colorado Sch Mines, Golden, CO 80401 USA. EM dmarr@mines.edu FU National Institutes of Health [1R01 AI079347-01]; National Institute of Health, National Institute of Allergy and Infectious Disease FX We acknowledge support from the National Institutes of Health under grant 1R01 AI079347-01 and the Intramural Research Program of the National Institute of Health, National Institute of Allergy and Infectious Disease and thank Kevin Roth, Allison Tyner and Maria Monroe for useful discussions. NR 35 TC 2 Z9 2 U1 1 U2 22 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 24 BP 4673 EP 4679 DI 10.1039/c4lc00863d PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AT6RG UT WOS:000345065700014 PM 25316326 ER PT J AU Zhao, BX Yao, YL Yang, K Rong, PF Huang, P Sun, K An, X Li, ZM Chen, XY Li, WW AF Zhao, Bingxia Yao, Yulian Yang, Kai Rong, Pengfei Huang, Peng Sun, Kang An, Xiao Li, Zhiming Chen, Xiaoyuan Li, Wanwan TI Mercaptopropionic acid-capped Mn2+:ZnSe/ZnO quantum dots with both downconversion and upconversion emissions for bioimaging applications SO NANOSCALE LA English DT Article ID MN-DOPED ZNSE; LIGHT-EMITTING-DIODES; SEMICONDUCTOR NANOCRYSTALS; HIGHLY LUMINESCENT; NANOPARTICLES; EMITTERS; ROUTE; PROBE AB Doped quantum dots (d-dots) can serve as fluorescent biosensors and biolabels for biological applications. Our study describes a synthesis of mercaptopropionic acid (MPA)-capped Mn2+:ZnSe/ZnO d-dots through a facile, cost-efficient hydrothermal route. The as-prepared water-soluble d-dots exhibit strong emission at ca. 580 nm, with a photoluminescence quantum yield (PLQY) as high as 31%, which is the highest value reported to date for such particles prepared via an aqueous route. They also exhibit upconversion emission when excited at 800 nm. With an overall diameter of around 6.7 nm, the d-dots could gain access to the cell nucleus without any surface decoration, demonstrating their promising broad applications as fluorescent labels. C1 [Zhao, Bingxia; Yao, Yulian; Sun, Kang; Li, Wanwan] Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, Shanghai 200240, Peoples R China. [Yang, Kai] Soochow Univ, SRMP, Suzhou 215123, Jiangsu, Peoples R China. [Yang, Kai] Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Jiangsu, Peoples R China. [Rong, Pengfei; Huang, Peng; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [An, Xiao] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 1, Shanghai 200080, Peoples R China. [Li, Zhiming] Wenzhou Med Univ, Affiliated Hosp 1, Dept Dermatol & Venereol, Wenzhou 325000, Zhejiang, Peoples R China. RP Sun, K (reprint author), Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, 800 Dongchuan Rd, Shanghai 200240, Peoples R China. EM ksun@sjtu.edu.cn; wwli@sjtu.edu.cn RI Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Basic Research Program of China (973 program) [2010CB933901, 2013CB733802]; National Natural Science Foundation of China [50902093, 81272987, 81371645]; Ph.D. Programs Foundation of the Ministry of Education of China [200802481131]; Medicine & Engineering Cross Research Foundation of Shanghai Jiao Tong University [YG2012MS61]; Zhejiang Provincial Natural Science Foundation of China [LY12H11011] FX This work was financially supported by the National Basic Research Program of China (973 program, 2010CB933901, 2013CB733802), the National Natural Science Foundation of China (project no. 50902093, 81272987, 81371645), a grant to Prof. Wanwan Li from the Ph.D. Programs Foundation of the Ministry of Education of China (project no. 200802481131), Medicine & Engineering Cross Research Foundation of Shanghai Jiao Tong University (project no. YG2012MS61), and Zhejiang Provincial Natural Science Foundation of China (project no. LY12H11011). We thank the Instrumental Analysis Center of SJTU for the assistance with TEM, XRD and XPS characterization. NR 47 TC 8 Z9 8 U1 16 U2 81 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2014 VL 6 IS 21 BP 12345 EP 12349 DI 10.1039/c4nr03490b PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AT5QQ UT WOS:000344997500015 PM 25189675 ER PT J AU Thornton, IM Horowitz, TS Bulthoff, HH AF Thornton, I. M. Horowitz, T. S. Buelthoff, H. H. TI Does action disrupt multiple object tracking? SO PERCEPTION LA English DT Meeting Abstract C1 [Thornton, I. M.] Univ Malta, Msida, Malta. [Horowitz, T. S.] NCI, Bethesda, MD 20892 USA. [Buelthoff, H. H.] Max Planck Inst, Munich, Germany. RI Bulthoff, Heinrich/J-6579-2012 OI Bulthoff, Heinrich/0000-0003-2568-0607 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 EI 1468-4233 J9 PERCEPTION JI Perception PY 2014 VL 43 IS 10 MA 44 BP 1128 EP 1128 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA AT8LS UT WOS:000345185400054 ER PT S AU Hoinka, J Berezhnoy, A Sauna, ZE Gilboa, E Przytycka, TM AF Hoinka, Jan Berezhnoy, Alexey Sauna, Zuben E. Gilboa, Eli Przytycka, Teresa M. BE Sharan, R TI AptaCluster - A Method to Cluster HT-SELEX Aptamer Pools and Lessons from Its Application SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, RECOMB2014 SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 18th Annual International Conference on Research in Computational Molecular Biology (RECOMB) CY APR 02-05, 2014 CL Carnegie Mellon Univ, Pittsburgh, PA SP Univ Pittsburgh, Dept Computat & Syst Biol, Int Soc Computat Biol, US Natl Sci Fdn, Biomed Cent GigaScience, Carnegie Mellons Lane Ctr Computat Biol HO Carnegie Mellon Univ ID IL-10 AB Systematic Evolution of Ligands by EXponential Enrichment (SELEX) is a well established experimental procedure to identify aptamers - synthetic single-stranded (ribo) nucleic molecules that bind to a given molecular target. Recently, new sequencing technologies have revolutionized the SELEX protocol by allowing for deep sequencing of the selection pools after each cycle. The emergence of High Throughput SELEX (HT-SELEX) has opened the field to new computational opportunities and challenges that are yet to be addressed. To aid the analysis of the results of HT-SELEX and to advance the understanding of the selection process itself, we developed AptaCluster. This algorithm allows for an efficient clustering of whole HT-SELEX aptamer pools; a task that could not be accomplished with traditional clustering algorithms due to the enormous size of such datasets. We performed HT-SELEX with Interleukin 10 receptor alpha chain (IL-10RA) as the target molecule and used AptaCluster to analyze the resulting sequences. AptaCluster allowed for the first survey of the relationships between sequences in different selection rounds and revealed previously not appreciated properties of the SELEX protocol. As the first tool of this kind, AptaCluster enables novel ways to analyze and to optimize the HT-SELEX procedure. Our AptaCluster algorithm is available as a very fast multiprocessor implementation upon request. C1 [Hoinka, Jan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Berezhnoy, Alexey; Gilboa, Eli] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. [Sauna, Zuben E.] Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Hemostasis, Div Hematol, Bethlehem, PA USA. RP Gilboa, E (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. EM EGilboa@med.miami.edu; przytyck@ncbi.nlm.nih.gov FU Intramural Research Program of the NIH; National Library of Medicine (JH, TMP); Laboratory of Hemostasis and the Center for Biologics Evaluation and Research; Food and Drug Administration's Modernization of Science program (ZES); Dodson estate and the Sylvester Comprehensive Cancer Center, Medical School, University of Miami ( AB and EG) FX This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine (JH, TMP), in part funds from the Laboratory of Hemostasis and the Center for Biologics Evaluation and Research, Food and Drug Administration's Modernization of Science program (ZES), and in part by bequest from the Dodson estate and the Sylvester Comprehensive Cancer Center, Medical School, University of Miami ( AB and EG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 19 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-05269-4; 978-3-319-05268-7 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2014 VL 8394 BP 115 EP 128 PG 14 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BB6XX UT WOS:000345119100009 ER PT S AU Makrogiannis, S Ferrucci, L AF Makrogiannis, Sokratis Ferrucci, Luigi BE Southern, SO Mentzer, MA RodriguezChavez, I Wotring, VE TI Software System for Computing Material and Structural Properties of Bone and Muscle in the Lower Extremity from pQCT SO SENSING TECHNOLOGIES FOR GLOBAL HEALTH, MILITARY MEDICINE, AND ENVIRONMENTAL MONITORING IV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring IV CY MAY 05-07, 2014 CL Baltimore, MD SP SPIE DE tissue quantification; image segmentation; pQCT AB Peripheral Quantitative Computed Tomography (pQCT) is a non-invasive imaging technology that is well-suited for quantification of bone structural and material properties. Because of its increasing use and applicability, the development of automated quantification methods for pQCT images is an appealing field of research. In this paper we introduce a software system for hard and soft tissue quantification in the lower leg using pQCT imaging data. The main stages of our approach are the segmentation and identification of bone, muscle and fat, and the computation of densitometric and geometric variables of each regional tissue type. Our system was validated against reference area and densitometric measurements over a set of test images and produced encouraging results. C1 [Makrogiannis, Sokratis] Delaware State Univ, Dept Math Sci, 1200 N Dupont Hwy, Dover, DE 19901 USA. [Makrogiannis, Sokratis; Ferrucci, Luigi] Natl Inst Hlth, Nat Insitute Aging, Baltimore, MD USA. RP Makrogiannis, S (reprint author), Delaware State Univ, Dept Math Sci, 1200 N Dupont Hwy, Dover, DE 19901 USA. EM smakrogiannis@desu.edu; ferruccilu@mail.nih.gov FU Intramural Research Program of the NIH; National Institute on Aging; Center for Research and Education in Optical Sciences and Applications of Dela; State University funded by NSF [CREST-8763] FX 'This research wa,s supported by the Intramural Research Program of the NIH, National Institute on Aging. We also acknowledge the support by the Center for Research and Education in Optical Sciences and Applications of Dela,ware State University funded by NSF CREST-8763. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-049-5 J9 PROC SPIE PY 2014 VL 9112 AR UNSP 911216 DI 10.1117/12.2050790 PG 6 WC Engineering, Biomedical; Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BB6WL UT WOS:000345075200016 ER PT J AU Sun, Y Zeng, Y Zhu, YC Feng, F Xu, WH Wu, CX Xing, B Zhang, WH Wu, PL Cui, LY Wang, RZ Li, F Chen, XY Zhu, ZH AF Sun, Yi Zeng, Yong Zhu, Yicheng Feng, Feng Xu, Weihai Wu, Chenxi Xing, Bing Zhang, Weihong Wu, Peiling Cui, Liying Wang, Renzhi Li, Fang Chen, Xiaoyuan Zhu, Zhaohui TI Application of Ga-68-PRGD2 PET/CT for alpha(v)beta(3)-integrin Imaging of Myocardial Infarction and Stroke SO THERANOSTICS LA English DT Article DE Ga-68-PRGD2; PET/CT; stroke; myocardial infarction; alpha(v)beta(3)-integrin; angiogenesis ID POSITRON-EMISSION-TOMOGRAPHY; INTEGRIN ALPHA(V)BETA(3); CANCER-PATIENTS; RGD PEPTIDES; SYSTEMATIC ANALYSIS; TUMOR ANGIOGENESIS; GLOBAL BURDEN; LUNG-CANCER; EXPRESSION; NEOVASCULATURE AB Purpose: Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of alpha(v)beta(3)-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed Ga-68-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)](2) (Ga-68-PRGD2) to evaluate the alpha(v)beta(3)-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT). Methods: With Institutional Review Board approval, 23 MI patients (3 days-2 years post-MI) and 16 stroke patients (3 days-13 years post-stroke) were recruited. After giving informed consent, each patient underwent a cardiac or brain PET/CT scan 30 min after the intravenous injection of Ga-68-PRGD2 in a dose of approximately 1.85 MBq (0.05 mCi) per kilogram body weight. Two stroke patients underwent repeat scans three months after the event. Results: Patchy Ga-68-PRGD2 uptake occurred in or around the ischemic regions in 20/23 MI patients and punctate multifocal uptake occurred in 8/16 stroke patients. The peak standardized uptake values (pSUVs) in MI were 1.94 +/- 0.48 (mean +/- SD; range, 0.62-2.69), significantly higher than those in stroke (mean +/- SD, 0.46 +/- 0.29; range, 0.15-0.93; P < 0.001). Higher Ga-68-PRGD2 uptake was observed in the patients 1-3 weeks after the initial onset of the MI/stroke event. The uptake levels were significantly correlated with the diameter of the diseases (r = 0.748, P = 0.001 for MI and r = 0.835, P = 0.003 for stroke). Smaller or older lesions displayed no uptake. Conclusions: Ga-68-PRGD2 uptake was observed around the ischemic region in both MI and stroke patients, which was correlated with the disease phase and severity. The different image patterns and uptake levels in MI and stroke patients warrant further investigations. C1 [Sun, Yi; Wu, Chenxi; Wu, Peiling; Li, Fang; Zhu, Zhaohui] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Nucl Med, Beijing 100730, Peoples R China. [Sun, Yi; Zeng, Yong; Zhu, Yicheng; Xu, Weihai; Wu, Chenxi; Xing, Bing; Zhang, Weihong; Wu, Peiling; Cui, Liying; Wang, Renzhi; Li, Fang; Zhu, Zhaohui] Peking Union Med Coll, Beijing 100021, Peoples R China. [Zeng, Yong] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Cardiol, Beijing 100730, Peoples R China. [Zhu, Yicheng; Xu, Weihai; Cui, Liying] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurol, Beijing 100730, Peoples R China. [Feng, Feng; Zhang, Weihong] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Radiol, Beijing 100730, Peoples R China. [Xing, Bing; Wang, Renzhi] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing 100730, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; zhuzhh@pumch.cn FU Major State Basic Research Development Program of China (973 Program) [2013CB733802, 2014CB744503]; National Natural Science Foundation of China [81171370, 81271614, 81371596, 30870725]; Capital Special Project for Featured Clinical Application [Z121107001012119]; Peking Union Medical College Hospital [PUMCH-2013-011]; Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported, in part, by Major State Basic Research Development Program of China (973 Program) (Grant Nos. 2013CB733802 and 2014CB744503), the National Natural Science Foundation of China projects (81171370, 81271614, 81371596 and 30870725), the Capital Special Project for Featured Clinical Application (Z121107001012119), Peking Union Medical College Hospital (PUMCH-2013-011), and the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 38 TC 10 Z9 10 U1 5 U2 14 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 8 BP 778 EP 786 DI 10.7150/thno.8809 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8YO UT WOS:000345215100002 PM 24955139 ER PT J AU Chi, C Du, Y Ye, J Kou, D Qiu, J Wang, J Tian, J Chen, X AF Chi, Chongwei Du, Yang Ye, Jinzuo Kou, Deqiang Qiu, Jingdan Wang, Jiandong Tian, Jie Chen, Xiaoyuan TI Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology SO THERANOSTICS LA English DT Review DE Optical molecular imaging; Intraoperative imaging-guided cancer surgery; Near-infrared fluorescence; Multi-modality Imaging; Indocyanine green ID SENTINEL LYMPH-NODE; NEAR-INFRARED FLUORESCENCE; INDOCYANINE GREEN FLUORESCENCE; EARLY GASTRIC-CANCER; CELL-PENETRATING PEPTIDES; HUMAN SERUM-ALBUMIN; IMMOBILIZED DIAGNOSTIC KIT; FLAP BREAST RECONSTRUCTION; CYSTEINE PROTEASE ACTIVITY; ACTIVITY-BASED PROBES AB Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. C1 [Chi, Chongwei; Du, Yang; Ye, Jinzuo; Tian, Jie] Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging Chinese Acad Sci, Beijing 100190, Peoples R China. [Chen, Xiaoyuan] NIBIB, NIH, Lab Mol Imaging & Nanomed, Bethesda, MD 20814 USA. [Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong] Gen Hosp Peoples Liberat Army, Dept Gen Surg, Beijing 100853, Peoples R China. RP Chen, XY (reprint author), NIBIB, NIH, Lab Mol Imaging & Nanomed, Bethesda, MD 20814 USA. EM tian@ieee.org; shawn.chen@nih.gov RI Tian, Jie/H-1190-2011; Tian, Jie/M-5675-2013 OI Tian, Jie/0000-0003-0498-0432; FU National Basic Research Program of China (973 Program) [2011CB707700, 2013CB733802, 2014CB744503]; National Natural Science Foundation of China [81227901, 61231004, 81371596]; National Key Technology R&D Program of China [2012BAI23B01] FX This paper is supported by the National Basic Research Program of China (973 Program) under Grant No. 2011CB707700, 2013CB733802, and 2014CB744503, the National Natural Science Foundation of China under Grant No. 81227901, 61231004, and 81371596, and the National Key Technology R&D Program of China under Grant No. 2012BAI23B01. NR 176 TC 61 Z9 64 U1 28 U2 102 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 11 BP 1072 EP 1084 DI 10.7150/thno.9899 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8XR UT WOS:000345212900002 PM 25250092 ER PT J AU Chuang, YJ Zhen, ZP Zhang, F Liu, F Mishra, JP Tang, W Chen, HM Huang, XL Wang, LC Chen, XY Xie, J Pan, ZW AF Chuang, Yen-Jun Zhen, Zipeng Zhang, Fan Liu, Feng Mishra, Jyoti P. Tang, Wei Chen, Hongmin Huang, Xinglu Wang, Lianchun Chen, Xiaoyuan Xie, Jin Pan, Zhengwei TI Photostimulable Near-Infrared Persistent Luminescent Nanoprobes for Ultrasensitive and Longitudinal Deep-Tissue Bio-Imaging SO THERANOSTICS LA English DT Article DE LiGa5O8:Cr3+ nanoparticles; near-infrared; persistent luminescence; photostimulated persistent luminescence; in vivo imaging ID QUANTUM DOTS; GENE-EXPRESSION; CELL MIGRATION; FLUORESCENT; CANCER; NANOPARTICLES; MACROPHAGES; METASTASIS; TRACKING; INVASION AB In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr3+ near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr3+ nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (similar to 15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging. C1 [Chuang, Yen-Jun; Liu, Feng; Pan, Zhengwei] Univ Georgia, Coll Engn, Athens, GA 30602 USA. [Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Xie, Jin] Univ Georgia, Dept Chem, Athens, GA 30602 USA. [Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Xie, Jin] Univ Georgia, Bioimaging Res Ctr, Athens, GA 30602 USA. [Zhang, Fan; Huang, Xinglu; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20852 USA. [Liu, Feng; Pan, Zhengwei] Univ Georgia, Dept Phys & Astron, Athens, GA 30602 USA. [Mishra, Jyoti P.; Wang, Lianchun] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Mishra, Jyoti P.; Wang, Lianchun] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Xie, J (reprint author), Univ Georgia, Coll Engn, Athens, GA 30602 USA. EM jinxie@uga.edu; panz@uga.edu RI Chen, Hongmin/B-9555-2011; OI Pan, Zhengwei/0000-0002-3854-958X FU NSF CAREER award [DMR-0955908]; NCI/NIH [5R00CA153772]; Intramural Research Program of NIBIB, NIH; NIH [R01HL093339, GM103390] FX This work was supported by a NSF CAREER award (DMR-0955908, Z.W.P.), an NCI/NIH R00 grant (5R00CA153772, J.X.), the Intramural Research Program of NIBIB, NIH (X.C.), a NIH R01 grant (R01HL093339, L.C.W.), and a NIH P41 grant GM103390, L.C.W.). We thank Rick Tarleton for allowing us to use the IVIS Lumina II imaging system and Mary Ard for TEM imaging. We also thank Just Nanotech Co., Ltd. (Taiwan) for wet grinding the nanoparticles. NR 39 TC 22 Z9 22 U1 13 U2 90 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 11 BP 1112 EP 1122 DI 10.7150/thno.9710 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8XR UT WOS:000345212900005 PM 25285164 ER PT J AU Yang, WM Laeyendecker, O Wendel, SK Zhang, B Sun, SS Zhou, JY Ao, MH Moore, RD Jackson, JB Zhang, H AF Yang, Weiming Laeyendecker, Oliver Wendel, Sarah K. Zhang, Bai Sun, Shisheng Zhou, Jian-Ying Ao, Minghui Moore, Richard D. Jackson, J. Brooks Zhang, Hui TI Glycoproteomic Study Reveals Altered Plasma Proteins Associated with HIV Elite Suppressors SO THERANOSTICS LA English DT Article DE HIV; elite suppressor; HAART; AIDS; glycoprotein; glycoproteomics; inflammation; immune activation ID IMMUNODEFICIENCY-VIRUS TYPE-1; ABDOMINAL AORTIC-ANEURYSM; ANTIRETROVIRAL THERAPY; NEUTRALIZING ANTIBODIES; INTERLEUKIN-6 RECEPTOR; VIRAL REPLICATION; MASS-SPECTROMETRY; IMMUNE-SYSTEM; SOLUBLE GP130; INFLAMMATION AB HIV elite suppressors (ES) or controllers are individuals achieving control of viremia by their natural immunological mechanisms without highly active antiretroviral therapy (HAART). Study of the mechanisms responsible for the immunological suppression of viremia in ES may lead to the detection of individuals with ES and the effective control of HIV infection. We hypothesize that plasma glycoproteins play essential roles in the immune system of ES since plasma proteins are critical and highly relevant in anti-viral immunity and most plasma proteins are glycoproteins. To examine glycoproteins associated with ES, plasma samples from ES individuals (n=20), and from individuals on HAART (n=20), with AIDS (n=20), and no HIV infection (n=10) were analyzed by quantitative glycoproteomics. We found that a number of glycoproteins changed between ES versus HAART, AIDS and HIV-individuals. In sharp contrast, the level of plasma glycoproteins in the HAART cohort showed fewer changes compared with AIDS and HIV-individuals. These results showed that although both ES and HAART effectively suppress viremia, ES appeared to profoundly affect immunologically relevant glycoproteins in plasma as consequence of or support for anti-viral immunity. Bioinformatic analysis revealed that altered proteins in ES plasma were mainly associated with inflammation. This analysis suggests that overlapping, while distinguishable, glycoprotein profiles for inflammation and immune activation appeared to be present between ES and non-ES (HAART+AIDS) cohorts, indicating different triggers for inflammation and immune activation between natural and treatment-related viral suppression. C1 [Yang, Weiming; Zhang, Bai; Sun, Shisheng; Zhou, Jian-Ying; Ao, Minghui; Jackson, J. Brooks; Zhang, Hui] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21231 USA. [Laeyendecker, Oliver; Moore, Richard D.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21231 USA. [Laeyendecker, Oliver; Wendel, Sarah K.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA. RP Zhang, H (reprint author), Johns Hopkins Univ, Dept Pathol, 4011 Smith Bldg,400 N Broadway, Baltimore, MD 21231 USA. EM hzhang32@jhmi.edu RI Yang, Weiming/D-8480-2017; OI Yang, Weiming/0000-0002-5023-2155; Laeyendecker, Oliver/0000-0002-6429-4760 FU National Institutes of Health (NIH), National Heart Lung and Blood Institute (NHLBI) grant, Programs of excellence in glycosciences (PEG) [P01HL107153]; National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID) grant for JHU-Guangxi, China Clinical Trials Unit [1U01 AI69482-01]; Division of Intramural Research NIAID; NIAID, National Institute of Child Health and Human Development, National Institute of Mental Health; Office of AIDS research of the NIH, DHHS [UM1 AI068613]; National Institutes of Health; National Cancer Institute, Clinical Proteomics Tumor Analysis Consortium [U24CA160036]; Early Detection Research Network (EDRN) [U01CA152813, U24CA115102]; NHLBI Proteomic Center [N01-HV-00240]; Open Access Promotion Fund of the Johns Hopkins University Libraries; [R01CA112314] FX This research was supported by National Institutes of Health (NIH), National Heart Lung and Blood Institute (NHLBI) grant, Programs of excellence in glycosciences (PEG, P01HL107153) and National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID) grant for JHU-Guangxi, China Clinical Trials Unit (1U01 AI69482-01) to Dr. J. Brooks Jackson. Dr. Laeyendecker and Ms. Wendel are supported by the Division of Intramural Research NIAID. We also acknowledge the support of Dr. Susan Eshleman and the HIV Prevention Trials Network (HPTN) sponsored by the NIAID, National Institute of Child Health and Human Development, National Institute of Mental Health, and the Office of AIDS research of the NIH, DHHS (UM1 AI068613). This work was also supported in part by the National Institutes of Health under grants and contracts of National Cancer Institute, Clinical Proteomics Tumor Analysis Consortium (U24CA160036), the Early Detection Research Network (EDRN, U01CA152813 and U24CA115102), and R01CA112314 and NHLBI Proteomic Center (N01-HV-00240). Publication of this article was funded in part by the Open Access Promotion Fund of the Johns Hopkins University Libraries. NR 53 TC 5 Z9 5 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 12 BP 1153 EP 1163 DI 10.7150/thno.9510 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8WI UT WOS:000345209500001 PM 25285165 ER PT J AU Chen, XL Wei, SS Ma, Y Lu, J Niu, G Xue, YH Chen, XY Yang, FQ AF Chen, Xiulan Wei, Shasha Ma, Ying Lu, Jie Niu, Gang Xue, Yanhong Chen, Xiaoyuan Yang, Fuquan TI Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer SO THERANOSTICS LA English DT Article DE Doxorubicin; multidrug resistance; ovarian cancer; quantitative proteomics; mitochondria ID P-GLYCOPROTEIN; STE20-RELATED KINASE; CELL-CULTURE; TUMOR-CELLS; AMINO-ACIDS; K562 CELLS; DOXORUBICIN; ADRIAMYCIN; APOPTOSIS; PROTEIN AB Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOPIMT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. C1 [Chen, Xiulan; Wei, Shasha; Yang, Fuquan] Chinese Acad Sci ences, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China. [Chen, Xiulan; Wei, Shasha; Yang, Fuquan] Chinese Acad Sci, Inst Biophys, Lab Prote, Beijing 100101, Peoples R China. [Wei, Shasha] Univ Chinese Acad Sci, Beijing 100049, Peoples R China. [Ma, Ying; Lu, Jie; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Xue, Yanhong] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China. RP Chen, XY (reprint author), Chinese Acad Sci ences, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China. EM shawn.chen@nih.gov; fqyang@ibp.ac.cn FU National Basic Research Program of China (973) [2010CB833703, 2012CB966803, 2011CB915501, 2013CB733802, 2014CB744503, 2014CBA02003]; National Natural Science Foundation of China [90919047, 81371596]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health; K. C. Wong Education Foundation, Hong Kong FX We would like to thank all members of the Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, for their supports in this research. This research was supported in part by the National Basic Research Program of China (973) (Grant nos. 2010CB833703, 2012CB966803, 2011CB915501, 2013CB733802 and 2014CB744503, 2014CBA02003), the National Natural Science Foundation of China (Grant nos. 90919047 and 81371596) and the intramural research program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. The authors gratefully acknowledge the support of K. C. Wong Education Foundation, Hong Kong. We would also like to thank the Center for Biological Imaging (CBI), Institute of Biophysics, Chinese Academy of Science, for our Confocal Microscopy work and acknowledge Chunli Jiang for her help of taking images. NR 39 TC 9 Z9 9 U1 0 U2 14 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 12 BP 1164 EP 1175 DI 10.7150/thno.8502 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8WI UT WOS:000345209500002 PM 25285166 ER PT B AU El Touny, LH Barkan, D Green, JE AF El Touny, Lara H. Barkan, Dalit Green, Jeffrey E. BE Hayat, MA TI The Role of Fibrosis in Tumor Progression and the Dormant to Proliferative Switch SO TUMOR DORMANCY, QUIESCENCE, AND SENESCENCE, VOL 2: AGING, CANCER, AND NONCANCER PATHOLOGIES LA English DT Article; Book Chapter DE Breast cancer; Cancer-associated fibroblast (CAF); Collagen-I and breast cancer dormancy; Extracellular matrix (ECM); Fibrosis; Hypoxia inducible factor (HIF); Lysyl oxidase (LOX); Proliferative switch; Tumor progression and dormancy; VEGF receptor 1(+) (VEGFR1(+)) ID BREAST-CANCER PROGRESSION; PROGNOSTIC-SIGNIFICANCE; METASTATIC OUTGROWTH; MAMMOGRAPHIC DENSITY; DUCTAL CARCINOMA; FIBROTIC FOCUS; LYSYL OXIDASE; COL-I; CELLS; COLLAGEN AB The extracellular matrix is known to play a pivotal role in normal breast development as well as tumorigenesis and breast cancer progression. Several lines of clinical evidence have associated the presence of fibrotic-like, activated stroma with poor therapeutic response and prognosis in breast cancer patients. Recent evidence suggests that extracellular changes are requisite for the formation of a pre-metastatic niche that provides a permissive environment for disseminated breast cancer cells to survive and proliferate. It is also thought that in the absence of favorable environmental cues at a metastatic site, disseminated tumor cells can be maintained in a dormant, metabolically active state until they encounter or modulate their surroundings into an environment that supports their proliferation. We have shown in vivo that the induction of lung fibrosis via adenoviral instillation of TGF alpha, which results in collagen-I accumulation, can induce the proliferation of an otherwise dormant breast cancer cell line (D2.0R). We have recapitulated this dormant-toproliferative switch by collagen-I supplementation in a three dimensional in vitro model of dormancy, suggesting that collagen-I is a major contributor to the overtly proliferative integrin alpha 1-dependent state of the D2.0R cells in fibrotic lungs. This work has highlighted the importance of the integrin beta 1 pathway and its downstream effectors as principal players C1 [El Touny, Lara H.; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Barkan, Dalit] Univ Haifa, Fac Sci, Dept Biol, IL-31999 Haifa, Israel. RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM jegreen@mail.nih.gov NR 40 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-94-007-7726-2; 978-94-007-7725-5 PY 2014 BP 155 EP 164 DI 10.1007/978-94-007-7726-2_16 D2 10.1007/978-94-007-7726-2 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA BB6PY UT WOS:000344927800018 ER PT B AU Rodrigues, NP Tipping, AJ AF Rodrigues, Neil P. Tipping, Alex J. BE Hayat, MA TI The Transcription Factor GATA2 Regulates Quiescence in Haematopoietic Stem and Progenitor Cells SO TUMOR DORMANCY, QUIESCENCE, AND SENESCENCE, VOL 2: AGING, CANCER, AND NONCANCER PATHOLOGIES LA English DT Article; Book Chapter DE CD34+CD38-cells; CD34+cord blood cells; Chemokine and cytokine signals; Common myeloid progenitors (CMPs); GATA2 expression; Granulocyte-macrophage progenitor (GMP) lineage; Haematopoietic stem cell (HSC); Haploinsuffi ciency of GATA2; Kinases CDK4 and CDK6; Quiescence-associated transcription factor MEF/ELF4 ID BONE-MARROW; C-MYB; MYELOID-LEUKEMIA; EXPRESSION; PROLIFERATION; CYCLE; PROTEIN; BLOOD; KIT AB Control of haematopoietic stem cell (HSC) proliferation is critical in preventing bone marrow failure or haematological malignancy. Understanding the mechanisms that balance the requirement to restrain excessive HSC proliferation while allowing for production of blood cells and maintenance of the HSC pool is therefore of substantial clinical interest. Herein we discuss the nature of HSC quiescence and the role of the zinc finger transcription factor GATA2 in regulating a gene expression program which reversibly confers quiescence on HSCs and committed progenitors. We present data extending previous observations of reduced HSC and progenitor functionality in the context of enforced GATA2 expression, and begin to demonstrate the molecular mechanisms by which the GATA2 program appears to function in restraining HSC and progenitor cell proliferation. Conversely, we also show that Gata2 haploinsufficiency impacts the quiescent program of HSCs and committed progenitors, demonstrating that HSC proliferation is exquisitely responsive to either up or down-regulation of GATA2 level. Finally, we discuss the clinical manifestations of loss-of-function GATA2 mutations and high GATA2 expression in the pre-malignant myelodys-plastic syndromes and myeloid leukaemia. C1 [Rodrigues, Neil P.] Boston Univ Med, Roger Williams Med Ctr, NIH, Ctr Biomed Res Excellence Stem Cell Biol, Providence, RI 02908 USA. [Rodrigues, Neil P.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Rodrigues, Neil P.] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA. [Tipping, Alex J.] UCL, Inst Canc, London WC1E 6DD, England. RP Tipping, AJ (reprint author), UCL, Inst Canc, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England. EM a.tipping@ucl.ac.uk NR 30 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-94-007-7726-2; 978-94-007-7725-5 PY 2014 BP 277 EP 288 DI 10.1007/978-94-007-7726-2_26 D2 10.1007/978-94-007-7726-2 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA BB6PY UT WOS:000344927800028 ER PT J AU George, AK Pinto, PA Rais-Bahrami, S AF George, Arvin K. Pinto, Peter A. Rais-Bahrami, Soroush TI Multiparametric MRI in the PSA Screening Era SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID TRANSRECTAL ULTRASOUND BIOPSY; LOCALIZED PROSTATE-CANCER; RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; 3 TESLA; FUSION BIOPSY; RESONANCE; CANDIDATES; INVASION; ACCURACY AB Prostate cancer remains significant public health concern amid growing controversies regarding prostate specific antigen (PSA) based screening. The utility of PSA has been brought into question, and alternative measures are investigated to remedy the overdetection of indolent disease and safeguard patients from the potential harms resulting from an elevated PSA. Multiparametric MRI of the prostate has shown promise in identifying patients at risk for clinically significant disease but its role within the current diagnostic and treatment paradigm remains in question. The current review focuses on recent applications of MRI in this pathway. C1 [George, Arvin K.; Pinto, Peter A.; Rais-Bahrami, Soroush] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP George, AK (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,2950-W,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA. EM arvin.george@nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research. The authors also thank the administrative support staff of the Urologic Oncology Branch, Center for Cancer Research, for assisting with the paper review and submission processes. NR 43 TC 14 Z9 14 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 465816 DI 10.1155/2014/465816 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AT0ZR UT WOS:000344663300001 ER PT J AU Kim, YJ Loria, A Zhao, XC Kleiner, DE Ghany, MG AF Kim, Yun Ju Loria, Anthony Zhao, Xiongce Kleiner, David E. Ghany, Marc G. TI Predictors of Autoimmune Hepatitis in Patients with Chronic Hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kim, Yun Ju; Loria, Anthony; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Zhao, Xiongce] NIDDK, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 36 BP 214A EP 214A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800037 ER PT J AU Angulo, P Kleiner, DE Dam-Larsen, S Adams, L Einar, BS Charatcharoenwitthaya, P Mills, PR Keach, JC Haflidadottir, S Bendtsen, F AF Angulo, Paul Kleiner, David E. Dam-Larsen, Sanne Adams, Leon Einar, Bjornsson S. Charatcharoenwitthaya, Phunchai Mills, Peter R. Keach, Jill C. Haflidadottir, Svanhildur Bendtsen, Flemming TI The prognostic relevance of liver histology features in nonalcoholic fatty liver disease: the PRELHIN study SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Angulo, Paul] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Dam-Larsen, Sanne; Bendtsen, Flemming] Univ Copenhagen, Dept Gastroenterol, Hvidovre Hosp, Copenhagen, Denmark. [Dam-Larsen, Sanne; Bendtsen, Flemming] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Adams, Leon] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Einar, Bjornsson S.; Haflidadottir, Svanhildur] Natl Univ Hosp Reykjavik, Sect Gastroenterol & Hepatol, Reykjavik, Iceland. [Charatcharoenwitthaya, Phunchai] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Mills, Peter R.] Gartnavel Royal Hosp, Glasgow, Lanark, Scotland. [Keach, Jill C.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. NR 0 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 59 BP 226A EP 227A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800060 ER PT J AU Pene, V Li, QS Sodroski, C Hsu, CS Liang, TJ AF Pene, Veronique Li, Qisheng Sodroski, Catherine Hsu, Ching-Sheng Liang, T. Jake TI Dynamic Association of DDX3X with Stress Granules and Lipid Droplets in Hepatocytes Confers Multiple Functions of DDX3X in Hepatitis C Virus Infection SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Pene, Veronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 62 BP 228A EP 228A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800063 ER PT J AU Townsend, KS Osinusi, A Nelson, AK Kohli, A Gross, C Polis, MA Pang, PS Sajadi, MM Subramanian, M McHutchison, JG Masur, H Kottilil, S AF Townsend, Kerry S. Osinusi, Anu Nelson, Amy K. Kohli, Anita Gross, Chloe Polis, Michael A. Pang, Phillip S. Sajadi, Mohammad M. Subramanian, Mani McHutchison, John G. Masur, Henry Kottilil, Shyam TI High Efficacy of Sofosbuvir/Ledipasvir for the Treatment of HCV Genotype 1 in Patients Coinfected With HIV on or off Antiretroviral therapy: Results from The NIAID ERADICATE Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Townsend, Kerry S.; Osinusi, Anu; Nelson, Amy K.; Polis, Michael A.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Osinusi, Anu; Sajadi, Mohammad M.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Kohli, Anita; Gross, Chloe] Frederick Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program,SAIC, Frederick, MD USA. [Kohli, Anita; Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Pang, Phillip S.; Subramanian, Mani; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 84 BP 240A EP 241A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801018 ER PT J AU Liangpunsakul, S Shah, V Sanyal, AJ Katz, BP Kamath, PS Puri, P Comerford, M Saberi, B Yu, ZS Ren, XW Chalasani, NP Crabb, DW Radaeva, S AF Liangpunsakul, Suthat Shah, Vijay Sanyal, Arun J. Katz, Barry P. Kamath, Patrick S. Puri, Puneet Comerford, Megan Saberi, Behnam Yu, Zhangsheng Ren, Xiaowei Chalasani, Naga P. Crabb, David W. Radaeva, Svetlana TI Clinical characteristics and outcomes of acute alcoholic hepatitis-early report from the Translational Research and Evolving Alcoholic hepatitis Treatment (TREAT) consortium SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Liangpunsakul, Suthat; Comerford, Megan; Chalasani, Naga P.; Crabb, David W.] Indiana Univ Sch Med IU, Dept Med, Div Gastroenterol Hepatol, Indianapolis, IN USA. [Shah, Vijay; Kamath, Patrick S.; Saberi, Behnam] Mayo Clin, Dept Med, Div Gastroenterol & Hepatol, Rochester, MN USA. [Sanyal, Arun J.; Puri, Puneet] Virginia Commonwealth Univ, Dept Med, Div Gastroenterol & Hepatol, Richmond, VA 23298 USA. [Katz, Barry P.; Yu, Zhangsheng; Ren, Xiaowei] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA. [Radaeva, Svetlana] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 139 BP 268A EP 268A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801073 ER PT J AU Brunt, EM Kleiner, DE Belt, PH Molleston, JP Schwimmer, JB Lavine, JE Neuschwander-Tetri, BA AF Brunt, Elizabeth M. Kleiner, David E. Belt, Patricia H. Molleston, Jean P. Schwimmer, Jeffrey B. Lavine, Joel E. Neuschwander-Tetri, Brent A. TI Pediatric Nonalcoholic Fatty Liver Disease (NAFLD): Histological Feature Changes Over Time in Paired Biopsies from the NASH CRN SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Brunt, Elizabeth M.] Washington Univ, Sch Med, St Louis, MO USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Belt, Patricia H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Molleston, Jean P.] Indiana Univ, Indianapolis, IN 46204 USA. [Schwimmer, Jeffrey B.] Univ Calif San Diego, San Diego, CA 92103 USA. [Lavine, Joel E.] Columbia Univ, New York, NY USA. [Neuschwander-Tetri, Brent A.] St Louis Univ, Sch Med, St Louis, MO USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 185 BP 290A EP 290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801119 ER PT J AU Long, MT Wang, N Larson, MG Mitchell, GF Palmisano, JN Ramachandran, VS Hoffmann, U Speliotes, EK Vita, JA Benjamin, EJ Fox, CS Hamburg, N AF Long, Michelle T. Wang, Na Larson, Martin G. Mitchell, Gary F. Palmisano, Joseph N. Ramachandran, Vasan S. Hoffmann, Udo Speliotes, Elizabeth K. Vita, Joseph A. Benjamin, Emelia J. Fox, Caroline S. Hamburg, Naomi TI The association of vascular function and non-alcoholic fatty liver disease: the Framingham Heart Study SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Long, Michelle T.] Boston Med Ctr, Boston, MA USA. [Long, Michelle T.; Larson, Martin G.; Ramachandran, Vasan S.; Benjamin, Emelia J.; Fox, Caroline S.; Hamburg, Naomi] NHLBI, Framingham Heart Study, Framingham, MA USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Na; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Palmisano, Joseph N.] Boston Univ, Sch Publ Hlth, Data Corrdinating Ctr, Boston, MA USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Speliotes, Elizabeth K.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 214 BP 306A EP 306A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801148 ER PT J AU Farci, P Zamboni, F Tice, AB Chen, ZC Engle, RE Diaz, G AF Farci, Patrizia Zamboni, Fausto Tice, Ashley B. Chen, Zhaochun Engle, Ronald E. Diaz, Giacomo TI Combined Gene and MicroRNA Expression Profiling of Hepatitis B Virus (HBV)-Associated Acute Liver Failure (ALF) Reveals a Dominant B-Cell-Driven Disease Signature SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Farci, Patrizia; Tice, Ashley B.; Chen, Zhaochun; Engle, Ronald E.] NIH, Infect Dis Lab, Hepat Pathogenesis Sect, Bethesda, MD 20892 USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 218 BP 308A EP 308A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801152 ER PT J AU Serti, E Park, H Liang, TJ Ghany, MG Rehermann, B AF Serti, Elisavet Park, Heiyoung Liang, T. Jake Ghany, Marc G. Rehermann, Barbara TI Rapid Decrease in Hepatitis C Virus Viremia by Direct Acting Antivirals Improves the Innate Immune Response to IFN alpha SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Serti, Elisavet; Park, Heiyoung; Liang, T. Jake; Ghany, Marc G.; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 225 BP 311A EP 311A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801159 ER PT J AU Canini, L Koh, C Cotler, S Yurday-Din, C Cooper, S Cory, D Haynes-Williams, V Winters, MA Choong, IC Hoofnagle, JH Glenn, J Heller, T Dahari, H AF Canini, Laetitia Koh, Christopher Cotler, Scott Yurdaydin, Cihan Cooper, Stewart Cory, David Haynes-Williams, Vanessa Winters, Mark A. Choong, Ingrid C. Hoofnagle, Jay H. Glenn, Jeffrey Heller, Theo Dahari, Harel TI Understanding hepatitis delta virus dynamics and antiviral efficacy of the prenylation inhibitor lonafarnib SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Canini, Laetitia; Dahari, Harel] Los Alamos Natl Lab, Los Alamos, NM USA. [Koh, Christopher; Haynes-Williams, Vanessa; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Cotler, Scott; Dahari, Harel] Loyola Univ, Med Ctr, Program Expt & Theoret Modeling, Dept Med,Div Hepatol, Maywood, IL 60153 USA. [Yurdaydin, Cihan] Ankara Univ, Dept Gastroenterol, TR-06100 Ankara, Turkey. [Cooper, Stewart] Calif Pacific Med Ctr, Div Gastroenterol, San Francisco, CA USA. [Cory, David; Winters, Mark A.; Choong, Ingrid C.] Eiger Biopharmaceut, San Carlos, CA USA. [Glenn, Jeffrey] Stanford Sch Med, Div Gastroenterol & Hepatol, Stanford, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 234 BP 317A EP 317A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801168 ER PT J AU Kapoor, R Kohli, A Sidharthan, S Sims, Z Petersen, TL Osinusi, A Nelson, AK Silk, R Kotb, C Sugarman, K Lam, BP Pang, PS Subramanian, M McHutchison, JG Masur, H Kottilil, S Rustgi, VK AF Kapoor, Rama Kohli, Anita Sidharthan, Sreetha Sims, Zayani Petersen, Tess L. Osinusi, Anu Nelson, Amy K. Silk, Rachel Kotb, Colleen Sugarman, Kate Lam, Brian P. Pang, Phillip S. Subramanian, Mani McHutchison, John G. Masur, Henry Kottilil, Shyam Rustgi, Vinod K. TI All Oral Treatment for Genotype 4 Chronic Hepatitis C Infection with Sofosbuvir and Ledipasvir: Interim Results from the NIAID SYNERGY Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kapoor, Rama; Kohli, Anita; Silk, Rachel; Kotb, Colleen] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD USA. [Sidharthan, Sreetha; Sims, Zayani; Petersen, Tess L.; Masur, Henry] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. [Osinusi, Anu; Nelson, Amy K.; Kottilil, Shyam] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Sugarman, Kate] Unity Hlth Care Inc, Washington, DC USA. [Lam, Brian P.] Inova Fairfax Med Campus, Ctr Liver Dis, Falls Church, VA USA. [Pang, Phillip S.; Subramanian, Mani; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Rustgi, Vinod K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 240 BP 321A EP 321A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801174 ER PT J AU Noureddin, M Kleiner, DE Zhao, XC Eccleston, JL Woolridge, D Noureddin, N Liang, TJ Hoofnagle, JH Heller, T AF Noureddin, Mazen Kleiner, David E. Zhao, Xiongce Eccleston, Jason L. Woolridge, Daniel Noureddin, Nabil Liang, T. Jake Hoofnagle, Jay H. Heller, Theo TI The Fraction of Bile Ducts Lost in Portal Areas Correlates with Degree of Fibrosis and Alkaline Phosphatase Levels in Patients with Primary Biliary Cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Kleiner, David E.; Zhao, Xiongce; Eccleston, Jason L.; Woolridge, Daniel; Noureddin, Nabil; Liang, T. Jake; Hoofnagle, Jay H.; Heller, Theo] NIH, Liver Dis Branch, Bethesda, MD USA. [Noureddin, Mazen] USC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 279 BP 339A EP 339A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801212 ER PT J AU Meissner, EG McLaughlin, M Matthews, LA Kanwar, B Bornstein, JD Kovacs, JA Kottilil, S Morse, CG AF Meissner, Eric G. McLaughlin, Mary Matthews, Lindsay A. Kanwar, Bittoo Bornstein, Jeffrey D. Kovacs, Joseph A. Kottilil, Shyam Morse, Caryn G. TI Longitudinal hepatic and PBMC gene expression profiling of HIV and/or HCV-infected patients with advanced liver disease treated with simtuzumab, an anti-LOXL2 antibody SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Meissner, Eric G.; McLaughlin, Mary; Matthews, Lindsay A.; Kovacs, Joseph A.; Kottilil, Shyam; Morse, Caryn G.] NIAID, NIH, Bethesda, MD 20892 USA. [Kanwar, Bittoo; Bornstein, Jeffrey D.] Gilead Sci, Foster City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 448 BP 421A EP 421A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801380 ER PT J AU Ouyang, XS Zhang, JY Feng, DC Cai, SY Garcia-Martinez, I Wang, FS Gao, B Mehal, WZ AF Ouyang, Xinshou Zhang, Ji-Yuan Feng, Dechun Cai, Shi-Ying Garcia-Martinez, Irma Wang, Fu-Sheng Gao, Bin Mehal, Wajahat Z. TI Low dose digoxin protects from NASH and alcoholic hepatitis in mice by inhibiting a ROS-HIF-1 alpha-inflammasome pathway SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ouyang, Xinshou; Zhang, Ji-Yuan; Cai, Shi-Ying; Garcia-Martinez, Irma; Mehal, Wajahat Z.] Yale Univ, New Haven, CT USA. [Feng, Dechun; Gao, Bin] NIAAA, NIH, Bethesda, MD USA. [Wang, Fu-Sheng] Beijing 302 Hosp, Inst Translat Hepatol, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 656 BP 518A EP 518A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802152 ER PT J AU Terrault, N Engle, RE Dodge, JL Freise, C Sherker, AH Farci, P Purcell, RH AF Terrault, Norah Engle, Ronald E. Dodge, Jennifer L. Freise, Chris Sherker, Averell H. Farci, Patrizia Purcell, Robert H. TI Hepatitis E Virus (HEV) Infection is Rare Cause of Hepatitis Among US Liver Transplant Recipients SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Terrault, Norah; Dodge, Jennifer L.; Freise, Chris] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Engle, Ronald E.; Farci, Patrizia; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Sherker, Averell H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 689 BP 534A EP 534A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802185 ER PT J AU Sehgal, R David, P Vyas, A Khanam, A Bhardwaj, A Rawal, P Hissar, S Patra, S Trivedi, SS Kottilil, S Sarin, SK Trehanpati, N AF Sehgal, Rashi David, Paul Vyas, Ashish Khanam, Arshi Bhardwaj, Ankit Rawal, Preety Hissar, Syed Patra, Sharda Trivedi, Shubha S. Kottilil, Shyam Sarin, Shiv K. Trehanpati, Nirupma TI Impaired monocyte and macrophage function in Hepatitis E Virus (HEV) infected pregnant women with Acute Liver Failure SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sehgal, Rashi; David, Paul; Vyas, Ashish; Khanam, Arshi; Bhardwaj, Ankit; Rawal, Preety; Hissar, Syed; Sarin, Shiv K.; Trehanpati, Nirupma] Inst Liver & Biliary Sci, New Delhi, India. [Patra, Sharda; Trivedi, Shubha S.] Lady Harding Med Coll, New Delhi, India. [Patra, Sharda; Trivedi, Shubha S.] Smt SK Hosp, New Delhi, India. [Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 737 BP 558A EP 558A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802233 ER PT J AU Lu, YY Rong, GH Feng, DC Wang, CP Chang, XJ Gao, XD Chen, Y Qu, JH Zeng, Z Wang, H Gao, B Yang, YP AF Lu, Yin Ying Rong, Guanghua Feng, Dechun Wang, Chunping Chang, Xiujuan Gao, Xudong Chen, Yan Qu, Jianhui Zeng, Zhen Wang, Hong Gao, Bin Yang, Yongping TI The role of Fyn in hepatic stellate cells activation and liver fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lu, Yin Ying; Rong, Guanghua; Wang, Chunping; Chang, Xiujuan; Gao, Xudong; Chen, Yan; Qu, Jianhui; Zeng, Zhen; Wang, Hong; Yang, Yongping] Beijing 302 Hosp, Ctr Therapeut Res Hepatocarcinoma, Beijing, Peoples R China. [Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 755 BP 566A EP 566A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802251 ER PT J AU Alao, H Fox, D Kokkinis, A Hadigan, C Grunseich, C Fischbeck, K Rotman, Y AF Alao, Hawwa Fox, Derrick Kokkinis, Angela Hadigan, Colleen Grunseich, Christopher Fischbeck, Kenneth Rotman, Yaron TI Hepatic Steatosis as a Component of Spinal and Bulbar Muscular Atrophy (SBMA, Kennedy's Disease) SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Alao, Hawwa; Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Hadigan, Colleen] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Fox, Derrick; Kokkinis, Angela; Grunseich, Christopher; Fischbeck, Kenneth] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 802 BP 586A EP 587A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802298 ER PT J AU Fischer, M Heinrich, S Andersen, JB Sprinzl, MF Gockel, I Woerns, MA Thorgeirsson, SS Galle, PR Lang, HK Marquardt, JU AF Fischer, Michael Heinrich, Stefan Andersen, Jesper B. Sprinzl, Martin F. Gockel, Ines Woerns, Marcus A. Thorgeirsson, Snorri S. Galle, Peter R. Lang, Hauke Marquardt, Jens U. TI The role of the tumor microenvironment for the CSC phenotype and progression of liver cancer: mechanistic findings and prognostic implications SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fischer, Michael; Sprinzl, Martin F.; Woerns, Marcus A.; Galle, Peter R.; Marquardt, Jens U.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55122 Mainz, Germany. [Heinrich, Stefan; Gockel, Ines; Lang, Hauke] Johannes Gutenberg Univ Mainz, Dept Gen Abdominal & Transplant Surg, D-55122 Mainz, Germany. [Andersen, Jesper B.; Thorgeirsson, Snorri S.; Marquardt, Jens U.] NCI, Lab Expt Carcinogenesis, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 906 BP 638A EP 638A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802402 ER PT J AU Marquardt, JU Gomez-Quiroz, LE Camacho, LOA Pinna, F Lee, YH Kitade, M Andersen, JB Breuhahn, K Galle, PR Factor, VM Thorgeirsson, SS AF Marquardt, Jens U. Gomez-Quiroz, Luis E. Camacho, Lucrecia O. Arreguin Pinna, Frederico Lee, Yun-Han Kitade, Mitsuteru Andersen, Jesper B. Breuhahn, Kai Galle, Peter R. Factor, Valentina M. Thorgeirsson, Snorri S. TI Curcumin targets stem-like liver cancer cells by NF-kB mediated inhibition of histone deacetylases SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Marquardt, Jens U.; Camacho, Lucrecia O. Arreguin; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55122 Mainz, Germany. [Marquardt, Jens U.; Gomez-Quiroz, Luis E.; Lee, Yun-Han; Kitade, Mitsuteru; Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, CCR, NIH, Bethesda, MD 20892 USA. [Pinna, Frederico; Breuhahn, Kai] Heidelberg Univ, Inst Pathol, Heidelberg, Germany. RI Pinna, Federico/A-8244-2017 OI Pinna, Federico/0000-0002-6815-110X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 909 BP 639A EP 639A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802405 ER PT J AU Shang, N Arteaga, M Stauffer, J Cotler, S Zhang, JW Qiu, W AF Shang, Na Arteaga, Maribel Stauffer, Jimmy Cotler, Scott Zhang, Jiwang Qiu, Wei TI FAK is required for c-Met/beta-catenin-driven hepatocarcinogenesis SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shang, Na; Arteaga, Maribel; Zhang, Jiwang; Qiu, Wei] Loyola Univ Chicago, Inst Oncol, Maywood, IL USA. [Stauffer, Jimmy] NCI, Frederick, MD 21701 USA. [Cotler, Scott] Loyola Univ Chicago, Maywood, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 936 BP 652A EP 652A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802432 ER PT J AU Rower, JE Meissner, EG Jimmerson, LC Osinusi, A Sims, Z Petersen, TL Bushman, L Wolfe, P McHutchison, JG Kottilil, S Kiser, JJ AF Rower, Joseph E. Meissner, Eric G. Jimmerson, Leah C. Osinusi, Anu Sims, Zayani Petersen, Tess L. Bushman, Lane Wolfe, Pamela McHutchison, John G. Kottilil, Shyam Kiser, Jennifer J. TI Plasma and Intracellular Ribavirin Pharmacokinetics and Concentration-Effect Analyses in Chronic Hepatitis C Virus Genotype 1 Patients Receiving Sofosbuvir plus Ribavirin in the NIAID SPARE Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Rower, Joseph E.; Jimmerson, Leah C.; Bushman, Lane; Wolfe, Pamela; Kiser, Jennifer J.] Univ Colorado, Aurora, CO USA. [Meissner, Eric G.; Osinusi, Anu; Sims, Zayani; Petersen, Tess L.; Kottilil, Shyam] NIAID, NIH, Bethesda, MD 20892 USA. [McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 967 BP 667A EP 668A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803016 ER PT J AU Fontana, RJ Hayashi, PH Reddy, R Kleiner, DE Phillips, T Barnhart, HX Talwalkar, JA Chalasani, NP Lee, WM Stolz, A Davern, TJ Watkins, PB Serrano, J AF Fontana, Robert J. Hayashi, Paul H. Reddy, Rajender Kleiner, David E. Phillips, Thomas Barnhart, Huiman X. Talwalkar, Jayant A. Chalasani, Naga P. Lee, William M. Stolz, Andrew Davern, Timothy J. Watkins, Paul B. Serrano, Jose TI Cholestatic Drug reactions are more likely to cause persistent liver injury and impaired Quality of Life during prolonged follow-up: Results from the DILIN Prospective study SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fontana, Robert J.] Univ Michigan Hosp, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Hayashi, Paul H.; Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC USA. [Reddy, Rajender] Univ Penn, Philadelphia, PA 19104 USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Phillips, Thomas; Barnhart, Huiman X.] Duke Clin Res Inst, Durham, NC USA. [Talwalkar, Jayant A.] Mayo Clin, Sch Med, Rochester, NY USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Stolz, Andrew] Univ So Carolina, Los Angeles, CA USA. [Davern, Timothy J.] Calif Pacific Med Ctr, San Francisco, CA USA. [Serrano, Jose] Nat Inst Diabet & Digest & Kidney Dis, Bethesday, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1067 BP 719A EP 720A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803116 ER PT J AU Russo, MW Norton, J Anderson, W Steuerwald, N Barnhart, HX Chalasani, NP Fontana, RJ Hayashi, PH Serrano, J Bonkovsky, HL AF Russo, Mark W. Norton, James Anderson, William Steuerwald, Nury Barnhart, Huiman X. Chalasani, Naga P. Fontana, Robert J. Hayashi, Paul H. Serrano, Jose Bonkovsky, Herbert L. TI Profiles of serum microRNAs in acute drug-induced liver injury and their prognostic significance SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Russo, Mark W.; Norton, James; Anderson, William; Steuerwald, Nury; Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Steuerwald, Nury] Carolinas Med Ctr, Levine Canc Inst, Charlotte, NC 28203 USA. [Barnhart, Huiman X.] Duke Univ, DCRI, Durham, NC USA. [Chalasani, Naga P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Hayashi, Paul H.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Serrano, Jose] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1076 BP 723A EP 724A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803125 ER PT J AU Ramirez, T Li, YM Feng, DC Xu, H Gao, B AF Ramirez, Teresa Li, Yongmei Feng, Dechun Xu, Huan Gao, Bin TI Aging Promotes Chronic Plus Binge Ethanol Feeding-Induced Liver Injury by Inhibiting Sirt1-Autophagy SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ramirez, Teresa; Li, Yongmei; Feng, Dechun; Xu, Huan; Gao, Bin] Natl Inst Alcohol & Alcoholism, Lab Liver Dis, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1112 BP 740A EP 741A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803161 ER PT J AU Jogasuria, A Gao, B You, M AF Jogasuria, Alvin Gao, Bin You, Min TI The Pivotal Role Played by Lipocalin-2 in Experimental Alcohol-Induced Fatty Liver Injury in Mice SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jogasuria, Alvin; You, Min] Northeast Ohio Med Univ NEOMED, Rootstown, OH USA. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1119 BP 744A EP 744A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803168 ER PT J AU Naguib, G Eccleston, JL Fujita, K Samala, N Walter, M Rotman, Y AF Naguib, Gihan Eccleston, Jason L. Fujita, Koji Samala, Niharika Walter, Mary Rotman, Yaron TI Association of IL-33/sST2 Axis with Non Alcoholic Steatohepatitis (NASH) Severity SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Naguib, Gihan; Eccleston, Jason L.; Fujita, Koji; Samala, Niharika; Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Walter, Mary] NIH, Clin Core Lab, Bethesda, MD 20892 USA. [Naguib, Gihan] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1137 BP 752A EP 752A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803186 ER PT J AU Wang, H Xu, MJ Bertola, A Gao, B AF Wang, Hua Xu, Ming-Jiang Bertola, Adeline Gao, Bin TI Long-term plus multiple binge ethanol feeding induces steatohepatitis and fibrosis in aged mice SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wang, Hua] Anhui Med Univ, Inst Liver Dis, Hefei, Peoples R China. [Wang, Hua; Xu, Ming-Jiang; Bertola, Adeline; Gao, Bin] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1168 BP 765A EP 766A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803217 ER PT J AU Wang, DQ de Bari, O Gao, B Wang, HH Portincasa, P Zhang, LS Ford, DA Neuschwander-Tetri, BA Tso, P AF Wang, David Q. de Bari, Ornella Gao, Bin Wang, Helen H. Portincasa, Piero Zhang, Linda S. Ford, David A. Neuschwander-Tetri, Brent A. Tso, Patrick TI Apolipoprotein (apo)AV deficiency exacerbates alcoholic liver injury, leading to a gradual progression from simple steatosis to steatohepatitis, and then to liver fibrosis in ethanol-fed mice SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wang, David Q.; de Bari, Ornella; Wang, Helen H.; Ford, David A.; Neuschwander-Tetri, Brent A.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Wang, David Q.; de Bari, Ornella; Wang, Helen H.; Ford, David A.; Neuschwander-Tetri, Brent A.] St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. [Portincasa, Piero] Univ Bari, Dept Biomed Sci & Human Oncol, Bari, Italy. [Zhang, Linda S.; Tso, Patrick] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1182 BP 772A EP 772A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803231 ER PT J AU Xu, MJ Cai, Y Altamirano, JT Chang, BX Wang, H Bertola, A Odena, G Lu, J Matsusue, K Kimura, S Gonzalez, FJ Bataller, R Gao, B AF Xu, Ming-Jiang Cai, Yan Altamirano, Jose T. Chang, Binxia Wang, Hua Bertola, Adeline Odena, Gemma Lu, Jim Matsusue, Kimihiko Kimura, Shioko Gonzalez, Frank J. Bataller, Ramon Gao, Bin TI Fat-specific Protein 27/CIDE-C Promotes Liver Injury in Chronic Plus Binge Ethanol Fed-mice And Human Alcoholic Hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Xu, Ming-Jiang; Chang, Binxia; Wang, Hua; Bertola, Adeline; Gao, Bin] NIAAA, NIH, Rockville, MD 20852 USA. [Xu, Ming-Jiang] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol 2, Beijing 100871, Peoples R China. [Cai, Yan; Kimura, Shioko; Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. [Altamirano, Jose T.] Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain. [Odena, Gemma; Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Lu, Jim] GoPath Diagnost LLC, Chicago, IL USA. [Matsusue, Kimihiko] Fukuoka Univ, Fac Pharmaceut Sci, Fukuoka 81401, Japan. [Bataller, Ramon] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RI Cai, Yan/P-4383-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1206 BP 783A EP 783A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803255 ER PT J AU Kirpich, I Falkner, KC Beier, JI Arteel, GE Ramsden, C Feldstein, AE McClain, CJ AF Kirpich, Irina Falkner, Keith C. Beier, Juliane I. Arteel, Gavin E. Ramsden, Christopher Feldstein, Ariel E. McClain, Craig J. TI Transient Receptor Potential Vanilloid 1 Gene Deficiency Ameliorates Hepatic Injury in a Mouse Model of Chronic-Binge-Induced Alcoholic Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kirpich, Irina; Falkner, Keith C.; McClain, Craig J.] Univ Louisville, Dept Med GI, Louisville, KY 40292 USA. [Beier, Juliane I.; Arteel, Gavin E.] Univ Louisville, Louisville, KY 40292 USA. [Ramsden, Christopher] NIH, Bethesda, MD 20892 USA. [Feldstein, Ariel E.] Univ Calif San Diego, San Diego, CA USA. [McClain, Craig J.] VA Med Ctr, Louisville, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1211 BP 785A EP 785A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803260 ER PT J AU Kirpich, I Umhau, J Vatsalya, V Schwandt, M Phillips, M Lionetti, T Falkner, KC Zhang, L Harwell, C George, D Heilig, M McClain, CJ AF Kirpich, Irina Umhau, John Vatsalya, Vatsalya Schwandt, Melanie Phillips, Monte Lionetti, Thomas Falkner, Keith C. Zhang, Lucy Harwell, Catey George, David Heilig, Markus McClain, Craig J. TI Interactions between the gut permeability, blood endotoxemia and liver injury in alcoholic patients during detoxification SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kirpich, Irina; Vatsalya, Vatsalya; Falkner, Keith C.; Zhang, Lucy; Harwell, Catey; McClain, Craig J.] Univ Louisville, Dept Med GI, Louisville, KY 40292 USA. [McClain, Craig J.] Robley Rex VA Med Ctr, Louisville, KY USA. [Umhau, John; Vatsalya, Vatsalya; Schwandt, Melanie; Phillips, Monte; Lionetti, Thomas; George, David; Heilig, Markus] NIAAA, Bethesda, MD USA. [Umhau, John] Whiteriver Indian Hosp, Whiteriver, AZ USA. [George, David] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1224 BP 791A EP 791A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803273 ER PT J AU Murakami, T Dominguez, CE Takyar, V Patel, K Boyer, TD Habib, S AF Murakami, Traci Dominguez, Cristian E. Takyar, Varun Patel, Krunal Boyer, Thomas D. Habib, Shahid TI Does the Alcoholic Liver Disease/Non-alcoholic fatty liver disease Index (ANI) predict mortality in Alcoholic Hepatitis? SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Murakami, Traci] Univ Arizona, Med Ctr, Tucson, AZ USA. [Boyer, Thomas D.; Habib, Shahid] Univ Arizona, Div Gastroenterol & Hepatol & Transplantat, Tucson, AZ USA. [Boyer, Thomas D.; Habib, Shahid] Univ Arizona, Liver Res Inst, Tucson, AZ USA. [Dominguez, Cristian E.; Takyar, Varun; Patel, Krunal] Univ Arizona, Dept Internal Med, Tucson, AZ USA. [Takyar, Varun] NIDDKD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1227 BP 792A EP 792A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803276 ER PT J AU Oishi, N Ji, JL Yamashita, T Ye, QH Kaneko, S Wang, XW AF Oishi, Naoki Ji, Juling Yamashita, Taro Ye, Qinghai Kaneko, Shuichi Wang, Xin W. TI Epithelial to mesenchymal transition affects the stemness of primary liver cancers SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Oishi, Naoki; Yamashita, Taro; Kaneko, Shuichi] Kanazawa Univ Hosp, Dept Gastroenterol, Kanazawa, Ishikawa, Japan. [Oishi, Naoki; Ji, Juling; Wang, Xin W.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Ye, Qinghai] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1339 BP 843A EP 843A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803387 ER PT J AU Samala, N Wright, EC Trenbeath, J Engle, RE Fryzek, N Alter, HJ Hoofnagle, JH Ghany, MG AF Samala, Niharika Wright, Elizabeth C. Trenbeath, Joni Engle, Ronald E. Fryzek, Nancy Alter, Harvey J. Hoofnagle, Jay H. Ghany, Marc G. TI Sero-prevalence of Hepatitis E In Patients With Chronic Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Samala, Niharika; Fryzek, Nancy; Hoofnagle, Jay H.; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Trenbeath, Joni; Alter, Harvey J.] NIH, Dept Transfus Med, Infect Dis Sect, Bethesda, MD 20892 USA. [Engle, Ronald E.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1558 BP 948A EP 948A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804121 ER PT J AU Tana, MM Alao, H Morris, N Walter, M Hattenbach, J Smyth, S Brychta, R Zhao, XC Rotman, Y AF Tana, Michele M. Alao, Hawwa Morris, Nevitt Walter, Mary Hattenbach, Jacob Smyth, Sarah Brychta, Robert Zhao, Xiongce Rotman, Yaron TI Fatigue of Compensated Chronic Liver Disease is associated with Altered Sleep Pattern and Melatonin Profile SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tana, Michele M.] UCSF, San Francisco, CA USA. [Tana, Michele M.; Alao, Hawwa; Morris, Nevitt; Walter, Mary; Hattenbach, Jacob; Smyth, Sarah; Brychta, Robert; Zhao, Xiongce; Rotman, Yaron] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1573 BP 955A EP 956A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804135 ER PT J AU Alao, H Paul, J Reger, RN Wright, EC Lu, K Childs, R Ghany, MG AF Alao, Hawwa Paul, Jeddeo Reger, Robert N. Wright, Elizabeth C. Lu, Kit Childs, Richard Ghany, Marc G. TI Anti-HBs loss and HBV Reactivation Between Reduced Intensity versus Myeloablative Hematopoietic Stem Cell Transplant Regimens SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Alao, Hawwa; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Baltimore, MD USA. [Paul, Jeddeo; Reger, Robert N.; Lu, Kit; Childs, Richard] NHLBI, NIH, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1619 BP 977A EP 978A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804182 ER PT J AU An, P Zeng, Z David, V Winkler, CA AF An, Ping Zeng, Zheng David, Victor Winkler, Cheryl A. TI The APOBEC3B gene deletion and hepatitis B virus-associated hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [An, Ping; Winkler, Cheryl A.] Leidos Biomed Res Inc, Frederick, MD USA. [Zeng, Zheng] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China. [David, Victor] NCI, Basic Res Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1625 BP 980A EP 981A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804188 ER PT J AU Chen, ZC Engle, RE Tice, AB Long, ZF Zamboni, F Diaz, G Farci, P AF Chen, Zhaochun Engle, Ronald E. Tice, Ashley B. Long, Zhifeng Zamboni, Fausto Diaz, Giacomo Farci, Patrizia TI Extensive Hepatitis B virus (HBV) Core Antigen Mutation Associated with Massive Intrahepatic Production of Germline Anti-core IgM and IgG Suggest a Major Role of Humoral Immunity in the Pathogenesis of HBV-Associated Acute Liver Failure (ALF) SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chen, Zhaochun; Engle, Ronald E.; Tice, Ashley B.; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Long, Zhifeng] Personal Diagnostix Inc, Gaithersburg, MD USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1720 BP 1026A EP 1026A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804282 ER PT J AU O'Brien, TR Kuhs, KA Pfeiffer, RM AF O'Brien, Thomas R. Kuhs, Krystle A. Pfeiffer, Ruth M. TI Per-Protocol Subgroup Analysis of Ledipasvir and Sofosbuvir for Chronic HCV in the ION-3 Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [O'Brien, Thomas R.; Kuhs, Krystle A.] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1753 BP 1042A EP 1043A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804315 ER PT J AU Sekhar, V Melis, M Diaz, G Engle, RE Kabat, J Tice, AB Altan-Bonnet, N Kleiner, DE Lusso, P Emerson, SU Zamboni, F Farci, P AF Sekhar, Vandana Melis, Marta Diaz, Giacomo Engle, Ronald E. Kabat, Juraj Tice, Ashley B. Altan-Bonnet, Nihal Kleiner, David E. Lusso, Paolo Emerson, Suzanne U. Zamboni, Fausto Farci, Patrizia TI TACSTD2 is a Novel HCV Host Cofactor that Regulates Claudin and Occludin Localization and is Downregulated in HCV-Associated Hepatocellular Carcinoma (HCC) SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sekhar, Vandana; Melis, Marta; Engle, Ronald E.; Tice, Ashley B.; Emerson, Suzanne U.; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, Bethesda, MD 20892 USA. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Kabat, Juraj] NIAID, Biol Imaging Facil, Res Technol Branch, Bethesda, MD 20892 USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Lusso, Paolo] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1774 BP 1052A EP 1053A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804336 ER PT J AU Vincent, RK Cazanave, SC Min, HK Mirshahi, F Kumar, DP Asgharpour, A Daita, K Murthy, KS Liang, TJ Sanyal, AJ AF Vincent, Robert K. Cazanave, Sophie C. Min, Hae-Ki Mirshahi, Faridoddin Kumar, Divya P. Asgharpour, Amon Daita, Kalyani Murthy, Karnam S. Liang, T. Jake Sanyal, Arun J. TI Hepatitis C Promotes Diabetes by Increasing Hepatic Insulin Resistance and Pancreatic Beta Cell Failure Via Suppression of Betatrophin a Novel Islet Cell Growth Factor SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Vincent, Robert K.; Cazanave, Sophie C.; Min, Hae-Ki; Mirshahi, Faridoddin; Kumar, Divya P.; Asgharpour, Amon; Daita, Kalyani; Murthy, Karnam S.; Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1780 BP 1055A EP 1055A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804342 ER PT J AU Noureddin, M Rotman, Y Thomas, E Zhang, F Park, H Rehermann, B Liang, TJ AF Noureddin, Mazen Rotman, Yaron Thomas, Emmanuel Zhang, Fang Park, Heiyoung Rehermann, Barbara Liang, T. Jake TI Treatment Response, IFNL3 (IL28B) and IFNL4 Genotype and Hepatic Expression of Interferons and Interferon-Stimulated Genes in Patients with Chronic Hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Rotman, Yaron; Thomas, Emmanuel; Zhang, Fang; Park, Heiyoung; Rehermann, Barbara; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Noureddin, Mazen] Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1783 BP 1057A EP 1057A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804345 ER PT J AU Serti, E Chepa-Lotrea, X Kim, YJ Fryzek, N Liang, TJ Ghany, MG Rehermann, B AF Serti, Elisavet Chepa-Lotrea, Xenia Kim, Yun Ju Fryzek, Nancy Liang, T. Jake Ghany, Marc G. Rehermann, Barbara TI NK Cell Function Normalizes after 4 Weeks of IFN-free Therapy of Chronic Hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Serti, Elisavet; Chepa-Lotrea, Xenia; Kim, Yun Ju; Fryzek, Nancy; Liang, T. Jake; Ghany, Marc G.; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1809 BP 1069A EP 1069A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804371 ER PT J AU Shrivastava, S Meissner, EG Funk, EK Poonia, S Shokeen, V Thakur, A Kottilil, S Sarin, SK Trehanpati, N AF Shrivastava, Shikha Meissner, Eric G. Funk, Emily K. Poonia, Seerat Shokeen, Virendra Thakur, Arun Kottilil, Shyam Sarin, Shiv K. Trehanpati, Nirupma TI Elevated hepatic lipid and interferon stimulated gene (ISG) expression in patients infected with hepatitis C virus genotype-3 (HCVGT-3) relative to patients with non-alcoholic steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shrivastava, Shikha; Meissner, Eric G.; Funk, Emily K.; Poonia, Seerat; Kottilil, Shyam] NIAID, Lab Immunoregulat, Bethesda, MD 20892 USA. [Shokeen, Virendra; Thakur, Arun; Sarin, Shiv K.; Trehanpati, Nirupma] Inst Liver & Biliary Sci, New Delhi, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1819 BP 1073A EP 1073A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804381 ER PT J AU Koh, C Yurdaydin, C Cooper, S Cory, D Dahari, H Haynes-Williams, V Winters, MA Bys, M Choong, IC Idilman, R Keskin, O Canini, L Pinto, P Wolff, EF Bishop, R Kleiner, DE Hoofnagle, JH Glenn, J Heller, T AF Koh, Christopher Yurdaydin, Cihan Cooper, Stewart Cory, David Dahari, Harel Haynes-Williams, Vanessa Winters, Mark A. Bys, Matthew Choong, Ingrid C. Idilman, Ramazan Keskin, Onur Canini, Laetitia Pinto, Peter Wolff, Erin F. Bishop, Rachel Kleiner, David E. Hoofnagle, Jay H. Glenn, Jeffrey Heller, Theo TI Prenylation inhibition with lonafarnib decreases hepatitis D levels in humans SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Koh, Christopher; Haynes-Williams, Vanessa; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Yurdaydin, Cihan; Idilman, Ramazan; Keskin, Onur] Ankara Univ, Dept Gastroenterol, TR-06100 Ankara, Turkey. [Cooper, Stewart] Calif Pacific Med Ctr, Div Hepatol, San Francisco, CA USA. [Cory, David; Winters, Mark A.; Bys, Matthew; Choong, Ingrid C.] Eiger Biopharmaceut, San Carlos, CA USA. [Dahari, Harel; Canini, Laetitia] Loyola Univ, Med Ctr, Div Hepatol, Maywood, IL 60153 USA. [Glenn, Jeffrey] Stanford Sch Med, Div Gastroenterol & Hepatol, Stanford, CA USA. [Pinto, Peter] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wolff, Erin F.] NICHD, Unit Reprod & Regenerat Med, NIH, Bethesda, MD USA. [Bishop, Rachel] NEI, Consult Serv Sect, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Glenn, Jeffrey; Heller, Theo] NIDDK, Bethesda, MD 20892 USA. [Glenn, Jeffrey; Heller, Theo] Stanford Sch Med, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1860 BP 1092A EP 1093A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804422 ER PT J AU Jones, S Marti, M Sims, Z Kohli, A Kattakuzhy, S Petersen, TL Silk, R Polis, MA Masur, H Kottilil, S Osinusi, A AF Jones, Sara Marti, Miriam Sims, Zayani Kohli, Anita Kattakuzhy, Sarah Petersen, Tess L. Silk, Rachel Polis, Michael A. Masur, Henry Kottilil, Shyam Osinusi, Anu TI Durability of Sustained Virologic Response in Hepatitis C Infected Patients Treated with IFN-Free DAA Regimens SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jones, Sara; Kohli, Anita; Kattakuzhy, Sarah; Silk, Rachel] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. [Marti, Miriam; Polis, Michael A.; Kottilil, Shyam; Osinusi, Anu] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Osinusi, Anu] Univ Maryland, Dept Infect Dis, Inst Human Virol, Baltimore, MD 21201 USA. [Sims, Zayani; Kohli, Anita; Petersen, Tess L.; Masur, Henry] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1971 BP 1159A EP 1159A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483805046 ER PT J AU Kaji, K Factor, VM Andersen, JB Korokhov, N Durkin, ME Conner, EA Thorgeirsson, SS AF Kaji, Kosuke Factor, Valentina M. Andersen, Jesper B. Korokhov, Nikolay Durkin, Marian E. Conner, Elizabeth A. Thorgeirsson, Snorri S. TI DNMT1 is essential for postnatal liver development SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kaji, Kosuke; Factor, Valentina M.; Andersen, Jesper B.; Korokhov, Nikolay; Durkin, Marian E.; Conner, Elizabeth A.; Thorgeirsson, Snorri S.] NCI, LEC, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 2023 BP 1184A EP 1185A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483805098 ER PT J AU Zheng, CY Baum, BJ AF Zheng, Changyu Baum, Bruce J. TI Integration of the Hybrid Adenoretroviral Vector AdLTR-luc Involves Both MoMLV Elements Flanking the Transgene SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE Hybrid vector; integration; LTR; adenoretrovirus; gene therapy ID MURINE LEUKEMIA-VIRUS; NUCLEAR-PORE COMPLEX; RETROVIRAL DNA; IN-VIVO; ADENOVIRUS DNA; POL GENE; CELLS; TRANSDUCTION; ASSOCIATION; EXPRESSION AB Vector delivery is still a bottleneck for gene therapy. To overcome some disadvantages of adenoviral and retroviral vectors, we developed a hybrid vector. This hybrid vector, AdLTR-luc, was created by adding two elements from Moloney murine leukemia virus (MoMLV) flanking the luciferase cDNA into an E1/E3-deleted, replication deficient serotype 5 adenovirus vector (Zheng et al., Nature Biotechnol, 2000), and demonstrated that the MoMLV element upstream of the luciferase cDNA was broken during the integration event. The purpose of the current study was to determine if the MoMLV element downstream of the luciferase cDNA was also broken when integration occurred. We used the same A5 cell clones (#10 and 11) from the earlier the paper along with restriction endonuclease digestions, plus Southern hybridization, and PCR. Southern hybridization indicated that the luciferase cDNA was intact in the cloned cells. Results from Xho I and Sal I digestions showed that integration occurred in cloned cells. Southern hybridizations after Nco I digestion suggested that there was a break in both MoMLV elements, upstream and downstream of the luciferase cDNA. After DNA digestion with Not I, hybridization analyses indicated that the MoMLV upstream element was broken during integration. Digestion of genomic DNA with either Xba I/Kpn I, Bam HI/Sac I, or Bam HI/Nco I demonstrated that the MoMLV downstream element was also broken during integration. A PCR assay was unable to amplify the junctional region between the downstream MoMLV element and the adenoviral E2B gene, consistent with a break in that element. Although AdLTR-luc integration is atypical (Zheng et al., Nature Biotechnol, 2000), the present results suggest that both MoMLV elements have important roles in this event. C1 [Zheng, Changyu; Baum, Bruce J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC 1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM czheng@mail.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health FX The Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, provided all support for this research. We would like to thank Mrs. Beverly Handelman for helping to clone the A5 cells. NR 27 TC 1 Z9 1 U1 1 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-1907 J9 INT J MED SCI JI Int. J. Med. Sci. PY 2014 VL 11 IS 8 BP 803 EP 809 DI 10.7150/ijms.9084 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AT0OY UT WOS:000344636300007 PM 24936143 ER PT J AU Cohen, S Barer, F Bar-Yehuda, S IJzerman, AP Jacobson, KA Fishman, P AF Cohen, Shira Barer, Faina Bar-Yehuda, Sara IJzerman, Adriaan P. Jacobson, Kenneth A. Fishman, Pnina TI A(3) Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action SO MEDIATORS OF INFLAMMATION LA English DT Article ID ELEVATING EXTRACELLULAR ADENOSINE; COLONY-STIMULATING FACTOR; G-CSF PRODUCTION; RHEUMATOID-ARTHRITIS; KAPPA-B; ENDOTOXEMIC MICE; CLINICAL-TRIAL; AGONIST; CF101; SUPPRESSION AB The A(3) adenosine receptor (A(3)AR) is overexpressed in inflammatory cells and in the peripheral blood mononuclear cells of individuals with inflammatory conditions. Agonists to the A(3)AR are known to induce specific anti-inflammatory effects upon chronic treatment. LUF6000 is an allosteric compound known to modulate the A(3)AR and render the endogenous ligand adenosine to bind to the receptor with higher affinity. The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. LUF6000 administration induced anti-inflammatory effect in 3 experimental animal models of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and concanavalin A induced liver inflammation in mice. The molecular mechanism of action points to deregulation of signaling proteins including PI3K, IKK, I kappa B, Jak-2, and STAT-1, resulting in decreased levels of NF-kappa B, known to mediate inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on the number of normal white blood cells and neutrophils. The anti-inflammatory effect of LUF6000, mechanism of action, and the differential effects on inflammatory and normal cells position this allosteric modulator as an attractive and unique drug candidate. C1 [Cohen, Shira; Barer, Faina; Bar-Yehuda, Sara; Fishman, Pnina] Can Fite BioPharma Ltd, IL-49170 Petah Tiqwa, Israel. [IJzerman, Adriaan P.] Leiden Univ, Leiden Acad Ctr Drug Res, Div Med Chem, NL-2300 RA Leiden, Netherlands. [Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Fishman, P (reprint author), Can Fite BioPharma Ltd, 10 Bareket St,POB 7537, IL-49170 Petah Tiqwa, Israel. EM pnina@canfite.co.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIDDK, NIH Intramural Research Program FX Kenneth A. Jacobson is supported by the NIDDK, NIH Intramural Research Program. NR 32 TC 2 Z9 2 U1 0 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2014 AR 708746 DI 10.1155/2014/708746 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AT1DF UT WOS:000344672700001 ER PT B AU Tsai, YC Moller, BE Adler, M Oyler, GA AF Tsai, Yien Che Moller, Brian E. Adler, Michael Oyler, George A. BE Foster, KA TI Molecular Basis for Persistence of Botulinum Neurotoxin: The Role of Intracellular Protein Degradation Pathways SO MOLECULAR ASPECTS OF BOTULINUM NEUROTOXIN, VOL 4 SE Current Topics in Neurotoxicity LA English DT Article; Book Chapter DE Bioterrorism; Botulinum neurotoxin; Ubiquitination; Deubiquitination; Persistence ID INDUCED PARALYSIS; UBIQUITIN LIGASE; LIGHT-CHAIN; TOXIN; SNAP-25; RECOVERY; RAT; CLEAVAGE; MUSCLE; 3,4-DIAMINOPYRIDINE AB A key aspect of botulinum neurotoxin biology, which underpins both the nature of botulism and the clinical success of therapeutic neurotoxin preparations, is the duration of effect of the neurotoxin on neurotransmitter release. There are seven different distinct serotypes of botulinum neurotoxins which exhibit a wide range in the duration of action or "persistence" after intoxications. The biological basis of persistence is beginning to be understood. One mechanism which underpins the duration of neurotoxin activity is survival of the light chain within the presynaptic terminal of the intoxicated neuron. For the neurotoxin light chain to remain in the presynaptic terminal maintaining the intoxication state, the bacterial protein must evade the two major pathways for cellular protein degradation, the ubiquitin-proteasome system degradation and the lysosomal/autophagy mechanism. A role for substrate cleavage products in persistence has also been suggested in perpetuating the intoxication state. These various ideas and the evidence for and against them are reviewed. The opportunity to modify the persistence of the neurotoxin and its therapeutic potential is also considered. C1 [Oyler, George A.] Synapt Res LLC, Baltimore, MD 21227 USA. [Oyler, George A.] Univ Nebraska, Lincoln, NE 68588 USA. [Tsai, Yien Che] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Moller, Brian E.; Adler, Michael] US Army Med Res Inst Chem Def, Neurobehav Toxicol Branch, Analyt Toxicol Div, Aberdeen, MD 21010 USA. RP Oyler, GA (reprint author), Synapt Res LLC, 1448 South Rolling Rd, Baltimore, MD 21227 USA. EM george@synapticresearch.com OI Tsai, Yien Che/0000-0001-9624-1092 NR 58 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-9454-6; 978-1-4614-9453-9 J9 CURR TOP NEUROTOX PY 2014 VL 4 BP 191 EP 205 DI 10.1007/978-1-4614-9454-6_9 D2 10.1007/978-1-4614-9454-6 PG 15 WC Biochemistry & Molecular Biology; Neurosciences; Toxicology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Toxicology GA BB6GC UT WOS:000344751500009 ER PT J AU Szatmary, AC Stuelten, CH Nossal, R AF Szatmary, Alex C. Stuelten, Christina H. Nossal, Ralph TI Improving the design of the agarose spot assay for eukaryotic cell chemotaxis SO RSC ADVANCES LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; POLYMORPHONUCLEAR LEUKOCYTES; MIGRATION PATTERNS; GRADIENTS; CANCER; DICTYOSTELIUM; RECRUITMENT; DIFFUSION; INVASION; SYSTEMS AB Migration of cells along gradients of effector molecules, i.e., chemotaxis, is necessary in immune response and is involved in development and cancer metastasis. The experimental assessment of chemotaxis thus is of high interest. The agarose spot assay is a simple tissue culture system used to analyze chemotaxis. Although direction sensing requires gradients to be sufficiently steep, how the chemical gradients developed in this assay change over time, and thus, under what conditions chemotaxis is plausible, has not yet been determined. Here, we use numerical solution of the diffusion equation to determine the chemoattractant gradient produced in the assay. Our analysis shows that, for the usual spot size, the lifetime of the assay is optimized if the chemoattractant concentration in the spot is initially 30 times the dissociation constant of the chemoattractant-receptor bond. This result holds regardless of the properties of the chemoattractant. With this initial concentration, the chemoattractant gradient falls to the minimum threshold for directional sensing at the same time that the concentration drops to the optimal level for detecting gradient direction. If a higher initial chemoattractant concentration is used, the useful lifetime of the assay is likely to be shortened because receptor saturation may decrease the cells' sensitivity to the gradient; lower initial concentrations would result in too little chemoattractant for the cells to detect. Moreover, chemoattractants with higher diffusion coefficients would sustain gradients for less time. Based on previous measurements of the diffusion coefficients of the chemoattractants EGF and CXCL12, we estimate that the assay will produce gradients that cells can sense for a duration of 10 h for EGF and 5 h for CXCL12. These gradient durations are comparable to what can be achieved with the Boyden chamber assay. The analysis presented in this work facilitates determination of suitable parameters for the assay, and can be used to assess whether observed cell motility is likely due to chemotaxis or chemokinesis. C1 [Szatmary, Alex C.; Nossal, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Stuelten, Christina H.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Szatmary, AC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM szatmaryac@mail.nih.gov FU Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Center for Cancer Research, NCI, National Institutes of Health FX This study was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Center for Cancer Research, NCI, National Institutes of Health. We appreciate the encouragement and comments given by Dr Carole Parent and also thank the members of the Nossal and Parent laboratories for helpful discussions. NR 43 TC 0 Z9 0 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 100 BP 57343 EP 57349 DI 10.1039/c4ra08572h PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA AT5QX UT WOS:000344998100093 PM 25530845 ER PT J AU Bokhari, AAB Mita-Mendoza, NK Fuller, A Pillai, AD Desai, SA AF Bokhari, Abdullah A. B. Mita-Mendoza, Neida K. Fuller, Alexandra Pillai, Ajay D. Desai, Sanjay A. TI High Guanidinium Permeability Reveals Dehydration-Dependent Ion Selectivity in the Plasmodial Surface Anion Channel SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID RED-BLOOD-CELLS; FALCIPARUM-INFECTED ERYTHROCYTES; X-RAY-MICROANALYSIS; MALARIA PARASITE; NUTRIENT-UPTAKE; RESISTANCE MECHANISM; PERMEATION PATHWAYS; HOST ERYTHROCYTE; DRUG-RESISTANCE; TRANSPORT AB Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC), an unusual ion channel linked to the conserved clag gene family. Although PSAC recognizes and transports a broad range of uncharged and charged solutes, it must efficiently exclude the small Na+ ion to maintain infected cell osmotic stability. Here, we examine possible mechanisms for this remarkable solute selectivity. We identify guanidiniumas an organic cation with high permeability into human erythrocytes infected with Plasmodium falciparum, but negligible uptake by uninfected cells. Transport characteristics and pharmacology indicate that this uptake is specifically mediated by PSAC. The rank order of organic and inorganic cation permeabilities suggests cation dehydration as the rate-limiting step in transport through the channel. The high guanidinium permeability of infected cells also allows rapid and stringent synchronization of parasite cultures, as required for molecular and cellular studies of this pathogen. These studies provide important insights into how nutrients and ions are transported via PSAC, an established target for antimalarial drug development. C1 [Bokhari, Abdullah A. B.; Mita-Mendoza, Neida K.; Fuller, Alexandra; Pillai, Ajay D.; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 48 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 741024 DI 10.1155/2014/741024 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AS2ZC UT WOS:000344143900001 ER PT J AU Ma, GD Yin, JW Fu, JW Luo, XD Zhou, HH Tao, H Cui, LL Li, Y Lin, ZX Zhao, B Li, Z Lin, JD Li, KS AF Ma, Guoda Yin, Jingwen Fu, Jiawu Luo, Xudong Zhou, Haihong Tao, Hua Cui, Lili Li, You Lin, Zhixiong Zhao, Bin Li, Zheng Lin, Juda Li, Keshen TI Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; MIR-137; VARIANT; MIR137; COGNITION; MICRORNA; RISK; SUSCEPTIBILITY; SYMPTOMS; CACNA1C AB Both genome wide association study (GWAS) and biochemical studies of Caucasian populations indicate a robust association between the miR-137 genetic variant rs1625579 and schizophrenia, but inconsistent results have been reported. To assay the association between this variant and schizophrenia, we genotyped 611 schizophrenic patients from Southern Chinese Han population for the risk single nucleotide polymorphism (SNP) rs1625579 using the SNaPshot technique and compared the clinical profiles of different genotypes. Additionally, a meta-analysis was performed using the combined sample groups from five casecontrol publications and the present study. Both the genotype and allele distributions of the rs1625579 SNP were significantly different between patients and controls (P = 0.036 and 0.026, SNP). TT genotype carriers showed slightly lower Brief Assessment of Cognition in Schizophrenia- (BACS-) derived working memory performance than G carriers (15.58 +/- 9.56 versus 19.71 +/- 8.18, P = 0.045). In the meta-analysis, we observed a significant association between rs1625579 and schizophrenia under different genetic models (all P < 0.05). The results of our study and meta-analysis provide convincing evidence that rs1625579 is significantly associated with schizophrenia. Furthermore, the miR-137 polymorphism influences the working memory performance of schizophrenic patients in a Chinese Han population. C1 [Ma, Guoda; Fu, Jiawu; Zhou, Haihong; Tao, Hua; Cui, Lili; Li, You; Zhao, Bin; Li, Keshen] Guangdong Med Coll, Inst Neurol, Zhanjiang 524001, Peoples R China. [Yin, Jingwen; Luo, Xudong; Lin, Zhixiong; Lin, Juda] Guangdong Med Coll, Affiliated Hosp, Dept Psychiat, Zhanjiang 524001, Peoples R China. [Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lin, JD (reprint author), Guangdong Med Coll, Affiliated Hosp, Dept Psychiat, Zhanjiang 524001, Peoples R China. EM linjuda@126.com; likeshen1971@126.com RI Li, Zheng/I-8016-2014; OI Li, Zheng/0000-0002-2978-2531; tao, hua/0000-0002-9506-5987; Cui, Lili/0000-0003-2150-3857 FU US-China Biomedical Collaborative Research Program [81261120404]; National Nature Science Foundation of China [31171219, 81271213, 81471294, 81271214]; Science and Technology Innovation Fund of Guangdong Medical College [STIF 201101] FX This work was supported by funding from the US-China Biomedical Collaborative Research Program (Grant no. 81261120404), the National Nature Science Foundation of China (Grant nos. 31171219, 81271213, 81471294, and 81271214), and the Science and Technology Innovation Fund of Guangdong Medical College (no. STIF 201101). NR 33 TC 1 Z9 1 U1 2 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 751267 DI 10.1155/2014/751267 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AT1BH UT WOS:000344667600001 ER PT J AU Pniewska, E Sokolowska, M Kuprys-Lipinska, I Przybek, M Kuna, P Pawliczak, R AF Pniewska, Ewa Sokolowska, Milena Kuprys-Lipinska, Izabela Przybek, Monika Kuna, Piotr Pawliczak, Rafal TI The Step Further to Understand the Role of Cytosolic Phospholipase A(2) Alpha and Group X Secretory Phospholipase A(2) in Allergic Inflammation: Pilot Study SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID NF-KAPPA-B; SMOOTH-MUSCLE-CELLS; MOUSE ASTHMA MODEL; HOUSE-DUST MITE; AIRWAY INFLAMMATION; EPITHELIAL-CELLS; GROUP IVA; ACTIVATION; MACROPHAGES; INVOLVEMENT AB Allergens, viral, and bacterial infections are responsible for asthma exacerbations that occur with progression of airway inflammation. cPLA(2)alpha and sPLA(2)X are responsible for delivery of arachidonic acid for production of eicosanoids-one of the key mediators of airway inflammation. However, cPLA(2)alpha and sPLA(2)X role in allergic inflammation has not been fully elucidated. The aim of this study was to analyze the influence of rDer p1 and rFel d1 and lipopolysaccharide (LPS) on cPLA(2)alpha expression and sPLA(2)X secretion in PBMC of asthmatics and in A549 cell line. PBMC isolated from 14 subjects, as well as A549 cells, were stimulated with rDer p1, rFel d1, and LPS. Immunoblotting technique was used to study the changes in cPLA(2)alpha protein expression and ELISA was used to analyze the release of sPLA(2)X. PBMC of asthmatics released more sPLA(2)X than those from healthy controls in the steady state. rDer p1 induced more sPLA(2)X secretion than cPLA(2)alpha protein expression. rFel d1 caused decrease in cPLA(2)alpha relative expression in PBMC of asthmatics and in A549 cells. Summarizing, Der p1 and Fel d1 involve phospholipase A(2) enzymes in their action. sPLA(2)X seems to be one of important PLA(2) isoform in allergic inflammation, especially caused by house dust mite allergens. C1 [Pniewska, Ewa; Przybek, Monika; Pawliczak, Rafal] Med Univ Lodz, Fac Biomed Sci & Postgrad Training, Dept Immunopathol, PL-90752 Lodz, Poland. [Sokolowska, Milena] NIH, Dept Crit Care Med, Crit Ctr, Bethesda, MD 20892 USA. [Kuprys-Lipinska, Izabela; Kuna, Piotr] Med Univ Lodz, Dept Internal Dis Asthma & Allergy, PL-90153 Lodz, Poland. RP Pawliczak, R (reprint author), Med Univ Lodz, Fac Biomed Sci & Postgrad Training, Dept Immunopathol, 7-9 Zeligowskiego St, PL-90752 Lodz, Poland. EM rafal.pawliczak@umed.lodz.pl RI Pawliczak, Rafal/S-9649-2016; Przybek, Monika/G-7673-2015 FU Medical University of Lodz [502-03/0-149-03/502-04-004, 502-03/0-149-03/502-04-021, 503/0-149-03/503-01]; Polish National Science Centre [DEC-2012/05/N/NZ5/02630]; [N N402 516939] FX The paper was supported from science budget for years 2010-2013 as research project (N N402 516939) and Medical University of Lodz Grants 502-03/0-149-03/502-04-004, 502-03/0-149-03/502-04-021, and 503/0-149-03/503-01. This paper was partially funded by Polish National Science Centre Grant no. DEC-2012/05/N/NZ5/02630. NR 40 TC 2 Z9 2 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 670814 DI 10.1155/2014/670814 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AS5BW UT WOS:000344288300001 ER PT J AU Cheng, Q Chang, JT Gwin, WR Zhu, J Ambs, S Geradts, J Lyerly, HK AF Cheng, Qing Chang, Jeffrey T. Gwin, William R. Zhu, Jun Ambs, Stefan Geradts, Joseph Lyerly, H. Kim TI A signature of epithelial-mesenchymal plasticity and stromal activation in primary tumor modulates late recurrence in breast cancer independent of disease subtype SO BREAST CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; BONE-MARROW; TENASCIN-C; CELL DISSEMINATION; ADJUVANT THERAPY; DORMANCY; PROTEIN; GROWTH; PROGRESSION; METASTASIS AB Introduction: Despite improvements in adjuvant therapy, late systemic recurrences remain a lethal consequence of both early-and late-stage breast cancer. A delayed recurrence is thought to arise from a state of tumor dormancy, but the mechanisms that govern tumor dormancy remain poorly understood. Methods: To address the features of breast tumors associated with late recurrence, but not confounded by variations in systemic treatment, we compiled breast tumor gene expression data from 4,767 patients and established a discovery cohort consisting of 743 lymph node-negative patients who did not receive systemic neoadjuvant or adjuvant therapy. We interrogated the gene expression profiles of the 743 tumors and identified gene expression patterns that were associated with early and late disease recurrence among these patients. We applied this classification to a subset of 46 patients for whom expression data from microdissected tumor epithelium and stroma was available, and identified a distinct gene signature in the stroma and also a corresponding tumor epithelium signature that predicted disease recurrence in the discovery cohort. This tumor epithelium signature was then validated as a predictor for late disease recurrence in the entire cohort of 4,767 patients. Results: We identified a novel 51-gene signature from microdissected tumor epithelium associated with late disease recurrence in breast cancer independent of the molecular disease subtype. This signature correlated with gene expression alterations in the adjacent tumor stroma and describes a process of epithelial to mesenchymal transition (EMT) and tumor-stroma interactions. Conclusions: Our findings suggest that an EMT-related gene signature in the tumor epithelium is related to both stromal activation and escape from disease dormancy in breast cancer. The presence of a late recurrence gene signature in the primary tumor also suggests that intrinsic features of this tumor regulate the transition of disseminated tumor cells into a dormant phenotype with the ability to outgrowth as recurrent disease. C1 [Cheng, Qing; Lyerly, H. Kim] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Chang, Jeffrey T.] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. [Gwin, William R.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Zhu, Jun] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Geradts, Joseph; Lyerly, H. Kim] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Cheng, Q (reprint author), Duke Univ, Med Ctr, Dept Surg, 203 Res Dr, Durham, NC 27710 USA. EM q.cheng@duke.edu; kim.lyerly@dm.duke.edu FU NIH [K12-CA100639-08]; Susan Komen Breast Cancer foundation [SAC100012] FX We gratefully acknowledge the contribution from the NCBI Gene Expression Omnibus and The Cancer Genome Atlas project providing molecular analysis data. We thank Sayan Mukherjee, Ph.D. (Departments of Statistical Science, Duke University) for his critical review and advice. We also thank Mark DeLong, Ph.D., Alan Cowles (Duke Institute for Genome Sciences and Policy, IT) and Jason C Barnette (Duke Surgery IT) for computational technique support. This work was supported in part by grant NIH K12-CA100639-08 to QC and Susan Komen Breast Cancer foundation SAC100012 to HKL. NR 66 TC 18 Z9 18 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 4 AR 407 DI 10.1186/s13058-014-0407-9 PG 13 WC Oncology SC Oncology GA AS5KQ UT WOS:000344310300015 PM 25060555 ER PT J AU Gierach, GL Li, H Loud, JT Greene, MH Chow, CK Lan, L Prindiville, SA Eng-Wong, J Soballe, PW Giambartolomei, C Mai, PL Galbo, CE Nichols, K Calzone, KA Olopade, OI Gail, MH Giger, ML AF Gierach, Gretchen L. Li, Hui Loud, Jennifer T. Greene, Mark H. Chow, Catherine K. Lan, Li Prindiville, Sheila A. Eng-Wong, Jennifer Soballe, Peter W. Giambartolomei, Claudia Mai, Phuong L. Galbo, Claudia E. Nichols, Kathryn Calzone, Kathleen A. Olopade, Olufunmilayo I. Gail, Mitchell H. Giger, Maryellen L. TI Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study SO BREAST CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; PARENCHYMAL PATTERNS; DIGITIZED MAMMOGRAMS; DENSITY; WOMEN; CARRIERS; CARCINOMA; IMAGES; ROC; POPULATION AB Introduction: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers. Methods: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject's digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject's belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model's discriminatory capacity. Results: In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density. Conclusions: Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography. C1 [Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, Hui; Lan, Li; Giger, Maryellen L.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Loud, Jennifer T.; Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chow, Catherine K.] Washington Radiol Associates, Potomac, MD USA. [Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Off Director, NIH, Bethesda, MD 20892 USA. [Eng-Wong, Jennifer] Genentech Inc, San Francisco, CA 94080 USA. [Soballe, Peter W.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Giambartolomei, Claudia] UCL, Genet Inst, London, England. [Galbo, Claudia E.] Uniformed Serv Univ Hlth Sci, Dept Radiol Sci, Bethesda, MD 20814 USA. [Galbo, Claudia E.] Walter Reed Natl Mil Med Ctr, Dept Radiol, Bethesda, MD USA. [Nichols, Kathryn] Westat Corp, Rockville, MD USA. [Calzone, Kathleen A.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Ctr Clin Canc Genet, Chicago, IL 60637 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gierach, GL (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA. EM gierachg@mail.nih.gov RI Gierach, Gretchen/E-1817-2016; OI Gierach, Gretchen/0000-0002-0165-5522; Giger, Maryellen/0000-0001-5482-9728 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute [NO2-CP-11019-50, NO2-CP-65504-50]; Westat, Inc., Rockville, MD; University of Chicago Breast SPORE [P50-CA125183]; DOE [DE-FG02-08ER6478]; NIH [S10 RR021039, P30 CA14599] FX This work and the research of Drs Gierach, Loud, Greene, Prindiville, Eng-Wong, Mai, Calzone and Gail, was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by support services contracts NO2-CP-11019-50 and NO2-CP-65504-50 with Westat, Inc., Rockville, MD. This research was also supported in part by the University of Chicago Breast SPORE P50-CA125183, DOE grant DE-FG02-08ER6478, NIH S10 RR021039, and P30 CA14599. The Breast Imaging Study (NCI Protocol #01-C-009); the Susceptibility to Breast Cancer Study (NCI Protocol #00-C-0079/NNMC Protocol #NNMC.2000.0010). Special thanks to all our study participants, whose cooperation was essential to the completion of this study. We are also indebted to Dr Ruthann Giusti, Clinical Genetics Branch, NCI, for her contributions to the initial development and implementation of the NCI Breast Imaging Study. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the National Institutes of Health, National Cancer Institute, Department of the Navy, Department of Defense, nor the US Government. NR 57 TC 12 Z9 12 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 4 AR 424 DI 10.1186/s13058-014-0424-8 PG 16 WC Oncology SC Oncology GA AS5KQ UT WOS:000344310300029 PM 25159706 ER PT J AU Rotunno, M Sun, XZ Figueroa, J Sherman, ME Garcia-Closas, M Meltzer, P Williams, T Schneider, SS Jerry, DJ Yang, XHR Troester, MA AF Rotunno, Melissa Sun, Xuezheng Figueroa, Jonine Sherman, Mark E. Garcia-Closas, Montserrat Meltzer, Paul Williams, Tyisha Schneider, Sallie Smith Jerry, D. Joseph Yang, Xiaohong R. Troester, Melissa A. TI Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status SO BREAST CANCER RESEARCH LA English DT Article ID INVOLUTING MAMMARY-GLAND; GENE-EXPRESSION; RISK-FACTORS; REPRODUCTIVE FACTORS; GENOMIC SIGNATURE; HORMONE-RECEPTOR; AGE; PREGNANCY; MICROENVIRONMENT; DIFFERENTIATION AB Introduction: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor-positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk. Methods: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status. Results: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. Conclusions: Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors. C1 [Rotunno, Melissa; Figueroa, Jonine; Sherman, Mark E.; Meltzer, Paul; Troester, Melissa A.] NCI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Sun, Xuezheng; Yang, Xiaohong R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Garcia-Closas, Montserrat] Inst Canc Res, London SW7 3RP, England. [Williams, Tyisha] Trinity Univ, Dept Biol, San Antonio, TX 78212 USA. [Schneider, Sallie Smith] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Jerry, D. Joseph] Pioneer Valley Life Sci Inst, Springfield, MA 01199 USA. [Rotunno, Melissa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Rotunno, M (reprint author), NCI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM rotunnom@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health; National Institute of Environmental Health Sciences; Breast Cancer and the Environment Research Program [U01 ES019472]; NCI [R01 CA138255]; Breast Specialized Program of Research Excellence (SPORE) [P50 CA058223]; Avon Foundation FX This research was supported by the following programs and grants: the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health; a National Institute of Environmental Health Sciences and NCI grant from the Breast Cancer and the Environment Research Program (U01 ES019472); NCI grant R01 CA138255; and a Breast Specialized Program of Research Excellence (SPORE) grant to the University of North Carolina (P50 CA058223). The Avon Foundation is gratefully acknowledged for financial support of this work. NR 52 TC 7 Z9 7 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 4 AR R74 DI 10.1186/bcr3689 PG 12 WC Oncology SC Oncology GA AS5KQ UT WOS:000344310300006 PM 25005139 ER PT J AU Togawa, K Ma, HY Sullivan-Halley, J Neuhouser, ML Imayama, I Baumgartner, KB Smith, AW Alfano, CM McTiernan, A Ballard-Barbash, R Bernstein, L AF Togawa, Kayo Ma, Huiyan Sullivan-Halley, Jane Neuhouser, Marian L. Imayama, Ikuyo Baumgartner, Kathy B. Smith, Ashley Wilder Alfano, Catherine M. McTiernan, Anne Ballard-Barbash, Rachel Bernstein, Leslie TI Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study SO BREAST CANCER RESEARCH LA English DT Article ID QUALITY-OF-LIFE; FOLLOW-UP; AXILLARY TREATMENT; NODE BIOPSY; CHEMOTHERAPY; PREVALENCE; CARCINOMA; SYMPTOMS; THERAPY; HEALTH AB Introduction: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. Methods: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). Results: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus >= 10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI >= 30 kg/m(2) (versus BMI <25 kg/m(2); HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. Conclusions: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema. C1 [Togawa, Kayo; Bernstein, Leslie] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90032 USA. [Togawa, Kayo; Ma, Huiyan; Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Neuhouser, Marian L.; Imayama, Ikuyo; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA. [Smith, Ashley Wilder; Alfano, Catherine M.; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Bernstein, L (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1975 Zonal Ave, Los Angeles, CA 90032 USA. EM lbernstein@coh.org FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, T32 CA09661]; National Institutes of Health [M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX This study was supported by National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228, and N01-PC-67010, and a training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the National Institutes of Health, Grant M01-RR-00037 and the University of New Mexico Grant NCRR M01-RR-0997. Data collection for the Women's CARE Study at the University of Southern California was supported by Grant N01-HD-3-3175 from the National Institute of Child Health and Human Development, and patient identification was supported in part by contract 050Q-8709-S1528 from the California Department of Health Services. NR 48 TC 13 Z9 13 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 4 AR 414 DI 10.1186/s13058-014-0414-x PG 15 WC Oncology SC Oncology GA AS5KQ UT WOS:000344310300022 PM 25145603 ER PT J AU Hwang, SY Zhang, MZ Zhang, CL Ma, BY Zheng, J Peng, ZM AF Hwang, Sang Youp Zhang, Mingzhen Zhang, Changlin Ma, Buyong Zheng, Jie Peng, Zhenmeng TI Carbon monoxide in controlling the surface formation of Group VIII metal nanoparticles SO CHEMICAL COMMUNICATIONS LA English DT Article ID PLATINUM NANOPARTICLES; SELECTIVE SYNTHESIS; CO ADSORPTION; SHAPE CONTROL; NANOCRYSTALS; CHEMISORPTION; KINETICS; NI(111); GROWTH; RAIRS AB Group VIII metal nanoparticles with variant morphologies were synthesized under a carbon monoxide atmosphere. The important roles of CO in determining the surface formation of growing particles were studied both by experiment and density functional theory (DFT) calculations, which suggest different growth mechanisms for these metals. C1 [Hwang, Sang Youp; Zhang, Mingzhen; Zhang, Changlin; Zheng, Jie; Peng, Zhenmeng] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA. [Ma, Buyong] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Peng, ZM (reprint author), Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA. EM zpeng@uakron.edu RI Peng, Zhenmeng/B-4278-2010; Zheng, Jie/B-5057-2013; Zhang, Changlin/I-9215-2016; Ma, Buyong/F-9491-2011 OI Peng, Zhenmeng/0000-0003-1230-6800; Zheng, Jie/0000-0003-1547-3612; Zhang, Changlin/0000-0002-1207-4264; Ma, Buyong/0000-0002-7383-719X FU UA; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Ohio Research Scholars Program Research Cluster on Surfaces in Advanced Materials FX This research was supported by the UA fund (Z.P.), and in part by Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E (B.M.). The HRTEM data were obtained at the (cryo) TEM facility at the Liquid Crystal Institute, Kent State University, supported by the Ohio Research Scholars Program Research Cluster on Surfaces in Advanced Materials. The authors thank Dr. Min Gao for technical support with the TEM experiments. NR 40 TC 4 Z9 4 U1 2 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2014 VL 50 IS 90 BP 14013 EP 14016 DI 10.1039/c4cc05770h PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AS0RO UT WOS:000343985600036 PM 25266416 ER PT J AU Iftikhar, H Ahmad, I Gan, SH Shaik, MM Iftikhar, N Nawaz, MS Greig, NH Kamal, MA AF Iftikhar, Hira Ahmad, Iqra Gan, Siew H. Shaik, Munvar M. Iftikhar, Naveed Nawaz, Muhammad S. Greig, Nigel H. Kamal, Mohammad A. TI Quinoline Derivatives: Candidate Drugs for a Class B G-Protein Coupled Receptor, the Calcitonin Gene-Related Peptide Receptor, a Cause of Migraines SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Calcitonin gene-related peptide; calcitonin receptor-like receptor; class B GPCR; docking; G-protein coupled receptor; migraine ID CRYSTAL-STRUCTURE; CGRP RECEPTOR; EXTRACELLULAR DOMAIN; ANTAGONISTS; DISCOVERY; IDENTIFICATION; SPECIFICITY; DIVERSITY; SEQUENCE; MK-0974 AB Class B G-protein coupled receptors are involved in a wide variety of diseases and are a major focus in drug design. Migraines are a common problem, and one of their major causative agents is the class B G-protein coupled receptor, Calcitonin gene-related peptide (CGRP) receptor, a target for competitive drug discovery. The calcitonin receptor-like receptor generates complexes with a receptor activity-modifying protein, which determines the type of receptor protein formed. The CGRP receptor comprises a complex formed from the calcitonin receptor-like receptor and receptor activity-modifying protein 1. In this study, an in silico docking approach was used to target the calcitonin receptor-like receptor in the bound form with receptor activity-modifying protein 1 (CGRP receptor), as well as in the unbound form. In both cases, the resulting inhibitors bound to the same cavity of the calcitonin receptor-like receptor. The twelve evaluated compounds were competitive inhibitors and showed efficient inhibitory activity against the CGRP receptor and Calcitonin receptor-like receptor. The two studied quinoline derivatives demonstrated potentially ideal inhibitory activity in terms of binding interactions and low range nano-molar inhibition constants. These compounds could prove helpful in designing drugs for the effective treatment of migraines. We propose that quinoline derivatives possess inhibitory activity by disturbing CGRP binding in the trigeminovascular system and may be considered for further preclinical appraisal for the treatment of migraines. C1 [Iftikhar, Hira] Natl Univ Sci & Technol, Atta Ur Rahman Sch Appl Biosci, Islamabad, Pakistan. [Ahmad, Iqra; Nawaz, Muhammad S.] COMSATS Inst Informat Technol, Dept Biosci, Islamabad, Pakistan. [Gan, Siew H.; Shaik, Munvar M.] Univ Sains Malaysia, Sch Med Sci, Ctr Human Genome, Kubang Kerian, Kelantan, Malaysia. [Iftikhar, Naveed] Poultry Res Inst, Rawalpindi, Pakistan. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Metabol & Enzymol Unit, Fundamental & Appl Biol Grp, Jeddah 21589, Saudi Arabia. RP Kamal, MA (reprint author), King Abdulaziz Univ, King Fahd Med Res Ctr, Metabol & Enzymol Unit, Fundamental & Appl Biol Grp, POB 80216, Jeddah 21589, Saudi Arabia. EM prof.makamal@lycos.com RI Shaik, Munvar/G-6458-2011; Gan, Hua/A-6266-2011 OI Shaik, Munvar/0000-0002-7053-9461; Gan, Hua/0000-0001-6470-3651 FU Intramural Research Program, NIA, NIH, USA; KFMRC, KAU, KSA FX NHG is supported by the Intramural Research Program, NIA, NIH, USA while MAK by KFMRC, KAU, KSA. NR 35 TC 0 Z9 0 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 7 BP 1130 EP 1139 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AS0UG UT WOS:000343993400003 PM 25230231 ER PT J AU Ashraf, GM Greig, NH Khan, TA Hassan, I Tabrez, S Shakil, S Sheikh, IA Zaidi, SK Akram, M Jabir, NR Firoz, CK Naeem, A Alhazza, IM Damanhouri, GA Kamal, MA AF Ashraf, Ghulam M. Greig, Nigel H. Khan, Taqi A. Hassan, Iftekhar Tabrez, Shams Shakil, Shazi Sheikh, Ishfaq A. Zaidi, Syed K. Akram, Mohammad Jabir, Nasimudeen R. Firoz, Chelaprom K. Naeem, Aabgeena Alhazza, Ibrahim M. Damanhouri, Ghazi A. Kamal, Mohammad A. TI Protein Misfolding and Aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Alzheimer's disease; amylin; amyloid-beta; amyloid precursor protein; islet amyloid polypeptide; neurofibrillary tangles; Parkinson's disease; protein folding; proteostasis; tau; tauopathy; type 2 diabetes mellitus; alpha-synuclein ID ISLET AMYLOID POLYPEPTIDE; PATHOLOGICAL ALPHA-SYNUCLEIN; BETA-SHEET STRUCTURE; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; IN-VITRO; SECONDARY STRUCTURE; INSULIN-RESISTANCE; EXTRACELLULAR TAU AB In general, proteins can only execute their various biological functions when they are appropriately folded. Their amino acid sequence encodes the relevant information required for correct three-dimensional folding, with or without the assistance of chaperones. The challenge associated with understanding protein folding is currently one of the most important aspects of the biological sciences. Misfolded protein intermediates form large polymers of unwanted aggregates and are involved in the pathogenesis of many human diseases, including Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM). AD is one of the most prevalent neurological disorders and has worldwide impact; whereas T2DM is considered a metabolic disease that detrementally influences numerous organs, afflicts some 8% of the adult population, and shares many risk factors with AD. Research data indicates that there is a widespread conformational change in the proteins involved in AD and T2DM that form beta-sheet like motifs. Although conformation of these beta-sheets is common to many functional proteins, the transition from alpha-helix to beta-sheet is a typical characteristic of amyloid deposits. Any abnormality in this transition results in protein aggregation and generation of insoluble fibrils. The abnormal and toxic proteins can interact with other native proteins and consequently catalyze their transition into the toxic state. Both AD and T2DM are prevalent in the aged population. AD is characterized by the accumulation of amyloid-beta (A beta) in brain, while T2DM is characterized by the deposition of islet amyloid polypeptide (IAPP, also known as amylin) within beta-cells of the pancreas. T2DM increases pathological angiogenesis and immature vascularisation. This also leads to chronic cerebral hypoperfusion, which results in dysfunction and degeneration of neuroglial cells. With an abundance of common mechanisms underpinning both disorders, a significant question that can be posed is whether T2DM leads to AD in aged individuals and the associations between other protein misfolding diseases. C1 [Ashraf, Ghulam M.; Tabrez, Shams; Sheikh, Ishfaq A.; Jabir, Nasimudeen R.; Firoz, Chelaprom K.; Damanhouri, Ghazi A.; Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,Biomed Res Ctr,NIH, Baltimore, MD 21224 USA. [Khan, Taqi A.] Sur Coll Appl Sci, Appl Biotechnol Dept, Sur 411, Oman. [Hassan, Iftekhar; Alhazza, Ibrahim M.] King Saud Univ, Coll Sci, Dept Zool, Riyadh 11451, Saudi Arabia. [Shakil, Shazi] Integral Univ, Dept Bioengn, Lucknow 226026, Uttar Pradesh, India. [Zaidi, Syed K.] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia. [Akram, Mohammad] King Abdulaziz Univ, Fac Sci & Arts Rabigh, Dept Biol, Rabigh 21911, Saudi Arabia. [Naeem, Aabgeena] Aligarh Muslim Univ, Fac Life Sci, Dept Biochem, Aligarh 202002, Uttar Pradesh, India. RP Ashraf, GM (reprint author), King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia. EM gashraf@kau.edu.sa; prof.makamal@lycos.com RI Ashraf, Ghulam Md/H-9485-2012; Tabrez, Shams/H-9476-2012; Chelapramkandy, Firoz/H-9487-2012; Zaidi, Syed Kashif /A-6160-2013; Rehumathbeevi, Jabir/H-9483-2012; Shakil, Shazi/K-4132-2015; Sheikh, Ishfaq/H-9611-2012; Faculty of, Sciences, KAU/E-7305-2017 OI Ashraf, Ghulam Md/0000-0002-9820-2078; Tabrez, Shams/0000-0003-4550-415X; Zaidi, Syed Kashif /0000-0003-2391-414X; Rehumathbeevi, Jabir/0000-0001-8548-7986; Shakil, Shazi/0000-0003-4075-9153; FU King Fahd Medical Research Center (KFMRC), King Abdulaziz University (Jeddah, Saudi Arabia); The Intramural Research Program of the National Inbstitute on Aging, National Institutes of Health FX The authors are grateful to (i) King Fahd Medical Research Center (KFMRC), King Abdulaziz University (Jeddah, Saudi Arabia), and (ii) The Intramural Research Program of the National Inbstitute on Aging, National Institutes of Health for support. Thanks are additionally due to Mohammad S Gazdar (Librarian, KFMRC) for providing assistance in searching the scientific literature. NR 182 TC 13 Z9 13 U1 3 U2 43 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 7 BP 1280 EP 1293 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AS0UG UT WOS:000343993400018 PM 25230234 ER PT J AU Yang, DW Kathawala, RJ Chufan, EE Patel, A Ambudkar, SV Chen, ZS Chen, X AF Yang, Danwen Kathawala, Rishil J. Chufan, Eduardo E. Patel, Atish Ambudkar, Suresh V. Chen, Zhe-Sheng Chen, Xiang TI Tivozanib reverses multidrug resistance mediated by ABCB1 (P-glycoprotein) and ABCG2 (BCRP) SO FUTURE ONCOLOGY LA English DT Article DE ABCB1; ABCG2; ABC transporter; multidrug resistance; tivozanib; tyrosine kinase inhibitor ID TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; RENAL-CELL CARCINOMA; SUBFAMILY-B MEMBER-1; PHASE-III TRIAL; BREAST-CANCER; DRUG-RESISTANCE; SOLID TUMORS; ANTITUMOR-ACTIVITY; ATP HYDROLYSIS AB Aim: This study aimed to investigate the mechanism of reversal of multidrug resistance mediated by ABC transporters with tivozanib (AV-951 and KRN-951). Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors. Materials & methods: ABCB1- and ABCG2-overexpressing cell lines were treated with respective substrate antineoplastic agents in the presence or absence of tivozanib. Results: The results indicate that tivozanib can significantly reverse ABCB1- mediated resistance to paclitaxel, vinblastine and colchicine, as well as ABCG2-mediated resistance to mitoxantrone, SN-38 and doxorubicin. Drug efflux assays showed that tivozanib increased the intracellular accumulation of substrates by inhibiting the ABCB1 and ABCG2 efflux activity. Furthermore, at a higher concentration, tivozanib inhibited the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2. Conclusion: We conclude that tivozanib at noncytotoxic concentrations has the previously unknown activity of reversing multidrug resistance mediated by ABCB1 and ABCG2 transporters. C1 [Yang, Danwen; Chen, Xiang] Xiangya Hosp, Dermatol Lab, Changsha, Hunan, Peoples R China. [Yang, Danwen; Kathawala, Rishil J.; Patel, Atish; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, New York, NY USA. [Chufan, Eduardo E.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chen, X (reprint author), Xiangya Hosp, Dermatol Lab, Changsha, Hunan, Peoples R China. EM chenxiangck@gmail.com RI Patel, Atish/J-4699-2014 OI Patel, Atish/0000-0002-5549-9166 FU RayBiotech; National Natural Science Foundation of China [81071290]; National Natural Science Foundation for Distinguished Young Scholars of China [81225013]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by funds from RayBiotech, the National Natural Science Foundation of China no. 81071290 (X Chen) and the National Natural Science Foundation for Distinguished Young Scholars of China no. 81225013 (X Chen). EE Chufan and SV Ambudkar were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 61 TC 5 Z9 6 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2014 VL 10 IS 11 BP 1827 EP 1841 DI 10.2217/FON.13.253 PG 15 WC Oncology SC Oncology GA AS1RK UT WOS:000344058100004 PM 24295377 ER PT J AU Pinsky, P AF Pinsky, Paul TI Re: Is the area under an ROC curve a valid measure of the performance of a screening or diagnostic test? SO JOURNAL OF MEDICAL SCREENING LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Pinsky, P (reprint author), NCI, 9609 Med Ctr Dr,Rm 5E108, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0969-1413 EI 1475-5793 J9 J MED SCREEN JI J. Med. Screen. PY 2014 VL 21 IS 4 BP 219 EP 219 DI 10.1177/0969141314548907 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AS6MS UT WOS:000344378200009 PM 25354869 ER PT J AU Barbosa, IG Bauer, ME Machado-Vieira, R Teixeira, AL AF Barbosa, Izabela Guimaraes Bauer, Moises Evandro Machado-Vieira, Rodrigo Teixeira, Antonio Lucio TI Cytokines in Bipolar Disorder: Paving the Way for Neuroprogression SO NEURAL PLASTICITY LA English DT Review ID NECROSIS-FACTOR-ALPHA; MAJOR DEPRESSION; MOOD DISORDERS; I DISORDER; PROINFLAMMATORY MARKERS; RECEPTOR ANTAGONIST; NEUROTROPHIC FACTOR; MULTIPLE-SCLEROSIS; GENE POLYMORPHISM; KOREAN POPULATION AB Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies. C1 [Barbosa, Izabela Guimaraes; Teixeira, Antonio Lucio] Univ Fed Minas Gerais, Fac Med, Div Neuropsiquiatria, Lab Interdisciplinar Invest Med, BR-30130100 Belo Horizonte, MG, Brazil. [Bauer, Moises Evandro] Pontificia Univ Catolica Rio Grande do Sul PUC RS, Inst Pesquisas Biomed, Lab Imunol Envelhecimento, BR-90610000 Porto Alegre, RS, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst Psiquiatria, LIM27, Lab Neurociencias, BR-01060970 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept Psiquiatria, BR-01060970 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20852 USA. [Teixeira, Antonio Lucio] Univ Fed Minas Gerais, IEAT, BR-31270901 Belo Horizonte, MG, Brazil. RP Barbosa, IG (reprint author), Univ Fed Minas Gerais, Fac Med, Div Neuropsiquiatria, Lab Interdisciplinar Invest Med, Ave Alfredo Balena,190 Santa Efigenia, BR-30130100 Belo Horizonte, MG, Brazil. EM izabelagb@gmail.com; altexr@gmail.com RI Bauer, Moises/J-9195-2015; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI Bauer, Moises/0000-0003-2957-1352; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU CNPq; Fapemig, Brazil; CAPES FX This work was partly funded by CNPq and Fapemig, Brazil. Dr. Barbosa is recipient of a CAPES postdoctorate scholarship. NR 108 TC 5 Z9 5 U1 2 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2014 AR 360481 DI 10.1155/2014/360481 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AS5MZ UT WOS:000344316100001 ER PT J AU Craiu, D Kaler, S Craiu, M AF Craiu, Dana Kaler, Stephen Craiu, Mihai TI Role of optic microscopy for early diagnosis of Menkes disease SO ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY LA English DT Article DE Menkes disease; hair microscopy; kinky hair; copper; pili torti; epilepsy ID ARGININOSUCCINIC ACIDURIA; BIOTINIDASE DEFICIENCY; COPPER; HAIR; DISORDERS; PERIOD AB We report the case of a male patient with a normal development in the first three months of life, presenting for global regression, central axial hypotonic syndrome, pyramidal syndrome, focal epileptic seizures, and a particular aspect of the hair almost absent, short, sparse, lightly colored, at age of five months, becoming coarse, twisted (kinky hair) by the age of 21 months. Different diseases associate similar neurological and macroscopic aspect of the hair (biotinidase deficiency, argininosuccinic aciduria, aminoaciduria, giant axonal neuropathy, trichothiodistrophy and Menkes syndrome). The microscopic aspect of the patient's hair showing normal hair, silver colored hair, hair shafts twisting 180 degrees, trichoclasis, and trichoptilosis, was highly characteristic for Menkes disease. Diagnosis was further supported by the low concentration of serum copper and ceruloplasmin and exclusion of other metabolic disorders with similar macroscopic aspect of the hair. Molecular genetic testing by multiplex PCR indicated deletion of exon 22 in the ATP7A gene situated in Xq21.1 region, consistent with the clinical and biochemical phenotype. Physicians should use microscopic evaluation of the hair more often when suspicion of Menkes disease is raised, aiming a narrow further diagnostic workup and early positive diagnosis and genetic advice for the affected families. C1 [Craiu, Dana] Carol Davila Univ Med & Pharm, Dept Neurol Pediat Neurol Psychiat Neurosurg Psyc, Discipline Pediat Neurol, Bucharest 041915, Romania. [Craiu, Dana] Alexandru Obregia Clin Psychiat Hosp, Clin Pediat Neurol, Bucharest, Romania. [Kaler, Stephen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD USA. [Craiu, Mihai] Carol Davila Univ Med & Pharm, Dept Pediat & Med Genet, Discipline Pediat, Bucharest 041915, Romania. [Craiu, Mihai] Alfred Rusescu Clin Pediat Hosp, Inst Mother & Child Hlth, Pediat Clin 2, Bucharest, Romania. RP Craiu, D (reprint author), Carol Davila Univ Med & Pharm, Dept Neurol Pediat Neurol Psychiat Neurosurg Psyc, Discipline Pediat Neurol, 10-12 Berceni Rd,Sect 4, Bucharest 041915, Romania. EM dcraiu@yahoo.com OI Craiu, Dana/0000-0003-4156-6812 NR 29 TC 0 Z9 0 U1 0 U2 1 PU EDITURA ACAD ROMANE PI BUCURESTI PA CALEA 13 SEPTEMBRIE NR 13, SECTOR 5, BUCURESTI 050711, ROMANIA SN 1220-0522 J9 ROM J MORPHOL EMBRYO JI Rom. J. Morphol. Embryol. PY 2014 VL 55 IS 3 BP 953 EP 956 PG 4 WC Developmental Biology SC Developmental Biology GA AS1KL UT WOS:000344040000028 PM 25329126 ER PT J AU Astefanoaei, C Creanga, D Pretegiani, E Optican, LM Rufa, A AF Astefanoaei, C. Creanga, D. Pretegiani, E. Optican, L. M. Rufa, A. TI DYNAMICAL COMPLEXITY ANALYSIS OF SACCADIC EYE MOVEMENTS IN TWO DIFFERENT PSYCHOLOGICAL CONDITIONS SO ROMANIAN REPORTS IN PHYSICS LA English DT Article DE visually guided saccades; infrared eye tracking system; chaos theory; computational tests ID CEREBELLAR ATAXIAS; CHAOS; SYSTEMS AB Saccadic eye movements of a normal subject were assessed through semi-quantitative analysis algorithms based on linear and non-linear test application in order to highlight the dynamics type characterizing saccadic neural system behavior. These movements were recorded during a simple visually-guided saccade test and one with a cognitive load involving button pressing to show a decision. Following the application of specific computational tests, chaotic dynamical trend dominancy was mostly revealed with some differences between the two saccade recording conditions: auto-correlation time was increased from 170 to 240 by cognitive task superposition and the Hurst exponent was enhanced from 0.52 to 0.76, denoting more persistence in the dynamics of saccadic system during increased neural activity related to cognitive task. C1 [Astefanoaei, C.; Creanga, D.] Univ Alexandru Ioan Cuza, Lab Biophys & Med Phys, Fac Phys, Iasi 700506, Romania. [Pretegiani, E.; Rufa, A.] Univ Siena, Dept Med Surg & Neurosci, Eye Tracking & Visual Applicat Lab EVALab, I-53100 Siena, Italy. [Optican, L. M.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Astefanoaei, C (reprint author), Univ Alexandru Ioan Cuza, Lab Biophys & Med Phys, Fac Phys, 11 Bd Carol 1, Iasi 700506, Romania. EM corina_astefanoaei@yahoo.com FU CERVISO FP7 IRSES-PEOPLE project [269263] FX This research was supported by CERVISO 269263 FP7 IRSES-PEOPLE project. NR 22 TC 2 Z9 2 U1 1 U2 7 PU EDITURA ACAD ROMANE PI BUCURESTI PA CALEA 13 SEPTEMBRIE NR 13, SECTOR 5, BUCURESTI 050711, ROMANIA SN 1221-1451 EI 1841-8759 J9 ROM REP PHYS JI Rom. Rep. Phys. PY 2014 VL 66 IS 4 BP 1038 EP 1055 PG 18 WC Physics, Multidisciplinary SC Physics GA AS7KM UT WOS:000344435100013 PM 25698890 ER PT S AU Dawsey, SM Fagundes, RB Jacobson, BC Kresty, LA Mallery, SR Paski, S van den Brandt, PA AF Dawsey, Sanford M. Fagundes, Renato B. Jacobson, Brian C. Kresty, Laura A. Mallery, Susan R. Paski, Shirley van den Brandt, Piet A. BE Giuli, R Umar, A TI Diet and esophageal disease SO 12TH OESO WORLD CONFERENCE: CANCERS OF THE ESOPHAGUS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 12th OESO World Conference - Cancers of the Esophagus CY AUG, 2013 CL UNESCO, Paris, FRANCE SP World Hlth Org, Int Agcy Res Canc, Natl Canc Inst HO UNESCO DE Barrett's esophagus; macronutrients; micronutrients; mate; nutrition; esophageal adenocarcinoma; OESO ID POLYCYCLIC AROMATIC-HYDROCARBONS; RANDOMIZED CLINICAL-TRIAL; BARRETTS-ESOPHAGUS; HIGH-RISK; PROSPECTIVE COHORT; NUTRITION SUPPORT; FRUIT CONSUMPTION; CANCER; ADENOCARCINOMA; MATE AB The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett's esophagus; micronutrients, trace elements, and risk of Barrett's esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient. C1 [Dawsey, Sanford M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Fagundes, Renato B.] Univ Fed Santa Maria, Dept Clin Med, Santa Maria, RS, Brazil. [Fagundes, Renato B.] Univ Fed Rio Grande do Sul, Programa Pos Grad Ciencias Gastroenterol, BR-90046900 Porto Alegre, RS, Brazil. [Jacobson, Brian C.] Boston Univ, Med Ctr, Boston, MA USA. [Kresty, Laura A.] Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Mallery, Susan R.] Ohio State Univ, Coll Dent, Div Oral Maxillofacial Pathol & Radiol, Columbus, OH 43210 USA. [Paski, Shirley] Univ Washington VA Puget Sound, Seattle, WA USA. [van den Brandt, Piet A.] Maastricht Univ, Med Ctr, Maastricht, Netherlands. RP Dawsey, SM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM annals@nyas.org FU NCI NIH HHS [R01 CA158319] NR 44 TC 3 Z9 3 U1 0 U2 9 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1325 BP 127 EP 137 DI 10.1111/nyas.12528 PG 11 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BB5DU UT WOS:000343712700014 PM 25266021 ER PT S AU Siriborvornratanakul, T AF Siriborvornratanakul, Thitirat BE Perales, FJ SantosVictor, J TI Multimodal Interface Towards Smartphones: The Use of Pico Projector, Passive RGB Imaging and Active Infrared Imaging SO ARTICULATED MOTION AND DEFORMABLE OBJECTS, AMDO 2014 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 8th International Conference on Articulated Motion and Deformable Objects (AMDO) CY JUL 16-18, 2014 CL Univ Illes Balears, Math & Comp Sci Dept, Palma de Mallorca, SPAIN SP Spanish Assoc Pattern Recognit & Artificial Intelligence, VICOM Tech, ANDROME Iberica S A, Expertise Cemtrum Digitale Media, iMinds HO Univ Illes Balears, Math & Comp Sci Dept DE Projector-camera; infrared; multimodal interface; smartphone AB This paper proposes a study regarding smartphone-oriented mobile devices capable of simultaneous passive RGB imaging and active infrared imaging for both projection and image sensing. Using RGB and infrared wavelengths together enables foreground interactive projection and background vision-based analysis to be done without unwanted crosstalk between the two spectrums or visible interruption to audiences. Our proposal includes detachable and rotatable mobile configuration designs, general computing paradigm and multimodal interface strategy; all are presented in a smartphone-oriented manner. Experiments are conducted to clarify efficiency and limitation of our proposal using a proof-of-concept setup. Despite of internal optic and mechanism which requires cooperation from technologys owner to fully accomplish, we believe that our proposal is useful and sustainable, enabling easy compatibility and maintenance with future mobile devices. C1 NIDA, Grad Sch Appl Stat, Bangkok 10240, Thailand. RP Siriborvornratanakul, T (reprint author), NIDA, Grad Sch Appl Stat, 118 SeriThai Rd, Bangkok 10240, Thailand. EM thitirat@as.nida.ac.th RI Santos-VIctor, Jose/K-2093-2012 OI Santos-VIctor, Jose/0000-0002-9036-1728 NR 14 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-08849-5; 978-3-319-08848-8 J9 LECT NOTES COMPUT SC PY 2014 VL 8563 BP 41 EP 50 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BB5HW UT WOS:000343879500005 ER PT J AU Kulmambetova, GN Imanbekova, MK Logvinenko, AA Sukashev, AT Filipenko, ML Ramanculov, EM AF Kulmambetova, Gulmira Nigmetzhanovna Imanbekova, Meruert Kuatbekovna Logvinenko, Andrey Alexeevich Sukashev, Adilbek Temirzhanovich Filipenko, Maxim Leonidovich Ramanculov, Erlan Mirhaidarovich TI Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Helicobacter pylori; gastritis; gastric cancer; polymorphism; cytokine ID HELICOBACTER-PYLORI INFECTION; PRECANCEROUS LESIONS; CHINESE POPULATION; ETHNIC-DIFFERENCES; CANCER DEVELOPMENT; SINGLE-NUCLEOTIDE; INCREASED RISK; INTERLEUKIN-1-BETA; METAANALYSIS; DISEASE AB Background: Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. Materials and Methods: The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Results: Association analysis of studied allelic variants and the development of gastritis in H. pylori-positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-T that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). Conclusions: The data from the current study showed that the genotype IL-1B -511T/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer. C1 [Kulmambetova, Gulmira Nigmetzhanovna; Imanbekova, Meruert Kuatbekovna; Ramanculov, Erlan Mirhaidarovich] Natl Ctr Biotechnol, Astana, Kazakhstan. [Logvinenko, Andrey Alexeevich; Sukashev, Adilbek Temirzhanovich] Natl Res Med Ctr, Astana, Kazakhstan. [Filipenko, Maxim Leonidovich] Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. RP Kulmambetova, GN (reprint author), Natl Ctr Biotechnol, Astana, Kazakhstan. EM gulmirakn@gmail.com FU Ministry of Education and Science of the Republic of Kazakhstan [0110RK00008] FX This study was funded by the Ministry of Education and Science of the Republic of Kazakhstan (grant 0110RK00008). The authors have no conflicts of interest. NR 35 TC 4 Z9 4 U1 1 U2 3 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2014 VL 15 IS 18 BP 7763 EP 7768 DI 10.7314/APJCP.2014.15.18.7763 PG 6 WC Oncology SC Oncology GA AR8OD UT WOS:000343833600043 PM 25292060 ER PT S AU Srivatsan, A Chen, XY AF Srivatsan, Avinash Chen, Xiaoyuan BE Pomper, MG Fisher, PB TI Recent Advances in Nanoparticle-Based Nuclear Imaging of Cancers SO EMERGING APPLICATIONS OF MOLECULAR IMAGING TO ONCOLOGY SE Advances in Cancer Research LA English DT Review; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; IRON-OXIDE NANOPARTICLES; IN-VIVO EVALUATION; STERICALLY STABILIZED LIPOSOMES; LONG-CIRCULATING LIPOSOMES; TUMOR-BEARING MICE; IN-111-DTPA-LABELED PEGYLATED LIPOSOMES; POLYETHYLENE-GLYCOL LIPOSOMES; GROWTH-FACTOR RECEPTOR; CARBON NANOTUBES AB Nuclear imaging techniques that include positron emission tomography (PET) and single-photon computed tomography have found great success in the clinic because of their inherent high sensitivity. Radionuclide imaging is the most popular form of imaging to be used for molecular imaging in oncology. While many types of molecules have been used for radionuclide-based molecular imaging, there has been a great interest in developing newer nanomaterials for use in clinic, especially for cancer diagnosis and treatment. Nanomaterials have unique physical properties which allow them to be used as imaging probes to locate and identify cancerous lesions. Over the past decade, a great number of nanoparticles have been developed for radionuclide imaging of cancer. This chapter reviews the different kinds of nanomaterials, both organic and inorganic, which are currently being researched for as potential agents for nuclear imaging of variety of cancers. Several radiolabeled multifunctional nanocarriers have been extremely successful for the detection of cancer in preclinical models. So far, significant progress has been achieved in nanoparticle structure design, in vitro/in vivo trafficking, and in vivo fate mapping by using PET. There is a great need for the development of newer nanoparticles, which improve active targeting and quantify new biomarkers for early disease detection and possible prevention of cancer. C1 [Srivatsan, Avinash; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 176 TC 10 Z9 10 U1 3 U2 32 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-411638-2 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2014 VL 124 BP 83 EP 129 DI 10.1016/B978-0-12-411638-2.00003-3 PG 47 WC Oncology SC Oncology GA BB6AT UT WOS:000344511500003 PM 25287687 ER PT J AU Wang, MY Monticone, RE Lakatta, EG AF Wang, Mingyi Monticone, Robert E. Lakatta, Edward G. TI Proinflammation of Aging Central Arteries: A Mini-Review SO GERONTOLOGY LA English DT Review DE Aging; Arterial remodeling; Proinflammation; Cellular phenotype ID SMOOTH-MUSCLE-CELLS; VASCULAR ADVENTITIAL FIBROBLASTS; AMERICAN-HEART-ASSOCIATION; AGE-DEPENDENT INCREASE; ANGIOTENSIN-II; NEOINTIMAL FORMATION; ENDOTHELIAL DYSFUNCTION; CELLULAR SENESCENCE; AEROBIC EXERCISE; OXIDATIVE STRESS AB Arterial aging is a cornerstone of organismal aging. The central arterial wall structurally and functionally remodels under chronic proinflammatory stress over a lifetime. The low-grade proinflamnnation that accompanies advancing age causes arterial wall thickening and stiffening. These structural and functional alterations are consequences of adverse molecular and cellular events, e.g. an increase in local angiotensin II signaling that induces an inflammatory phenotypic shift of endothelial and smooth muscle cells. Thus, interventions to restrict proinflammatory signaling are a rational approach to delay or prevent age-associated adverse arterial remodeling. (C) 2014 S. Karger AG, Basel C1 [Wang, Mingyi; Monticone, Robert E.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, BRC, Baltimore, MD 21224 USA. RP Wang, MY (reprint author), NIA, Cardiovasc Sci Lab, NIH, BRC, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mingyiw@grc.nia.nih.gov; lakattae@grc.nia.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 82 TC 7 Z9 8 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X EI 1423-0003 J9 GERONTOLOGY JI Gerontology PY 2014 VL 60 IS 6 BP 519 EP 529 DI 10.1159/000362548 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AR7XO UT WOS:000343790400006 PM 25171100 ER PT J AU Hokey, DA Wachholder, R Darrah, PA Bolton, DL Barouch, DH Hill, K Dheenadhayalan, V Schwander, S Godin, CS Douoguih, M Pau, MG Seder, RA Roederer, M Sadoff, JC Sizemore, D AF Hokey, David A. Wachholder, Robert Darrah, Patricia A. Bolton, Diane L. Barouch, Dan H. Hill, Krystal Dheenadhayalan, Veerabadran Schwander, Stephan Godin, C. Steven Douoguih, Macaya Pau, Maria Grazia Seder, Robert A. Roederer, Mario Sadoff, Jerald C. Sizemore, Donata TI A nonhuman primate toxicology and immunogenicity study evaluating aerosol delivery of AERAS-402/Ad35 vaccine Evidence for transient t cell responses in peripheral blood and robust sustained responses in the lungs SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE tuberculosis; vaccine; adenovirus; aerosol; mucosal; toxicology; cellular; T cell; primate ID DRUG-RESISTANT TUBERCULOSIS; CYSTIC-FIBROSIS; RECOMBINANT ADENOVIRUS; RESPIRATORY-TRACT; DENDRITIC CELLS; PULMONARY TUBERCULOSIS; IMMUNE-RESPONSES; GENE-THERAPY; GUINEA-PIGS; BCG AB Bacille Calmette-Guerin (BCG), the only licensed vaccine for the prevention of tuberculosis (TB), provides only limited protection against certain forms of Mycobacterium tuberculosis (Mtb) infection. While infection with Mtb can be treated with antibiotics, the therapy is expensive, toxic, and requires several months for treatment. In addition, the emergence of drug resistant strains limits the impact of antibiotics and underlines the importance of developing a more effective vaccine to control this disease. Given that pulmonary TB is the most common form of the disease, a vaccine capable of inducing lung-resident immunity may be advantageous for combating this infection. New advances in pulmonary delivery make this route of vaccination feasible and affordable. Here, we evaluate the safety and immunogenicity of an aerosolized Ad35-based vaccine, AERAS-402, delivered to the lungs in nonhuman primates as part of a GLP acute and chronic toxicology and safety study. In this study, animals received three high doses (1 x 10(11) vp) of AERAS-402 by inhalation via a nebulizer at 1-week intervals. Aerosol delivery of AERAS-402 resulted in an increase in relative lung weights as well as microscopic findings in the lungs, mediastinal lymph nodes, bronchus-associated lymphatic tissue, and the naso-oropharynx that were consistent with the induction of an immune response during the acute phase. These findings resolved by the chronic phase and were considered to be non-adverse. Furthermore, we observed transient vaccine-specific immune responses in the peripheral blood as well as sustained high-level polyfunctional CD4(+) and CD8(+) T cell responses in the bronchoalveolar lavage fluid of vaccinated nonhuman primates. The data suggest that pulmonary delivery of Ad35-based vaccines can be safe and can induce potent lung-resident immunity. C1 [Hokey, David A.; Wachholder, Robert; Hill, Krystal; Dheenadhayalan, Veerabadran] Aeras, Rockville, MD 20850 USA. [Darrah, Patricia A.; Seder, Robert A.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Bolton, Diane L.] US Mil HIV Res Program, Silver Spring, MD USA. [Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Schwander, Stephan] Rutgers Sch Publ Hlth, Piscataway, NJ USA. [Godin, C. Steven] Smithers Avanza, Gaithersburg, MD USA. [Douoguih, Macaya; Pau, Maria Grazia; Sadoff, Jerald C.] Crucell Holland BV, Leiden, Netherlands. [Sizemore, Donata] USA MRIID, Ft Detrick, MD USA. RP Hokey, DA (reprint author), Aeras, Rockville, MD 20850 USA. EM dhokey@aeras.org FU Bill and Melinda Gates Foundation; NIH [AI095985, AI078526, AI096040] FX This work was funded by the Bill and Melinda Gates Foundation and the NIH (grant numbers AI095985, AI078526, and AI096040). NR 52 TC 7 Z9 7 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PY 2014 VL 10 IS 8 BP 2199 EP 2210 DI 10.4161/hv.29108 PG 12 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA AS5NW UT WOS:000344318300015 PM 25424923 ER PT J AU Dobrovolskaia, MA Neun, BW Clogston, JD Grossman, JH McNeil, SE AF Dobrovolskaia, Marina A. Neun, Barry W. Clogston, Jeffrey D. Grossman, Jennifer H. McNeil, Scott E. TI Choice of method for endotoxin detection depends on nanoformulation SO NANOMEDICINE LA English DT Article DE endotoxin; interference; in vitro assay; limulus amoebocyte lysate; lipopolysaccharide nanoparticles; rabbit pyrogen test ID AMEBOCYTE; HEMODIALYSIS; REMOVAL; TESTS AB Aims: Many nanoparticles interfere with traditional tests to quantify endotoxin. The aim of this study was to compare the performance of limulus amoebocyte lysate (LAL) formats on clinical-grade nanoformulations, to determine whether there were disparate results among formats and to test the applicability of an alternative bioassay (the macrophage activation test [MAT]) for resolving discrepancies, if observed. Materials & methods: Clinical-grade nanoformulations were tested using turbidimetric, gel-clot and chromogenic LAL. Formulations that cause a discrepancy among LAL tests were also tested by the MAT. Results & conclusion: The gel-clot LAL method cannot be relied upon to resolve discrepancies among LAL tests for certain nanoformulations. No one LAL format was shown to be optimal for all the tested clinical-grade nanoformulations. The tested alternative bioassay (the MAT) was useful for verifying LAL findings, but only for those nanoformulations not carrying/including cytotoxic drugs. C1 [Dobrovolskaia, Marina A.; Neun, Barry W.; Clogston, Jeffrey D.; Grossman, Jennifer H.; McNeil, Scott E.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Dobrovolskaia, MA (reprint author), Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD 21702 USA. EM marina@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute, NIH [HHSN261200800001E] FX The study was supported in whole or in part by federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 29 TC 7 Z9 7 U1 0 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2014 VL 9 IS 12 BP 1847 EP 1856 DI 10.2217/NNM.13.157 PG 10 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AR9OQ UT WOS:000343904800007 PM 24359551 ER PT J AU Lapi, D Mastantuono, T Cesarelli, M D'Addio, G Romano, M Bifulco, P Gorbach, A Colantuoni, A AF Lapi, D. Mastantuono, T. Cesarelli, M. D'Addio, G. Romano, M. Bifulco, P. Gorbach, A. Colantuoni, A. GP IEEE TI Blood Flow Oscillatory Patterns in Single Vessels of Rat Pial Microcirculation Evaluated by Laser Speckle Imaging SO 2014 8TH CONFERENCE OF THE EUROPEAN STUDY GROUP ON CARDIOVASCULAR OSCILLATIONS (ESGCO) LA English DT Proceedings Paper CT 8th Conference of the European-Study-Group-on-Cardiovascular-Oscillations (ESGCO) CY MAY 25-28, 2014 CL Trento, ITALY SP Univ Studi Trento, Biomed Technologies, Univ Studi Milano, Provincia Autonoma Trento & Bruno Kessler Fdn, Healthcare Res Implementat Program, European Soc Hypertens, IEEE EMBS, European Study Grp Cardiovascular Oscillat DE Pial microcirculation; blood flow oscillatory patterns; power spectrum; wavelet transform; frequency components ID PERFUSION; DOPPLER AB The present study was aimed to assess blood flow oscillatory patterns in rat pial microcirculation by laser speckle imaging. Laser speckle methods provides maps of cerebral blood flow with elevated temporal and spatial resolution. The study was carried out on male Wistar rats. An open cranial window was prepared on the parietal region. Pial arterioles were classified by Strahler method in five orders by fluorescence microscopy. The blood flow oscillatory patterns were determined by laser speckle imaging in single pial vessels. Power spectrum analysis was performed by wavelet methods under baseline conditions. Arterioles and venules were characterized by blood flow oscillations with frequency components in the ranges 0.005 - 0.0095 Hz, 0.0095 - 0.02 Hz, 0.02-0.15 Hz, 0.15-0.5 Hz. Arterioles showed oscillations with higher total power and higher spectral density in the range 0.02 -0.15 when compared with venules. Laser speckle imaging allowed us to evaluate arteriolar and venular blood flow oscillations. C1 [Lapi, D.; Mastantuono, T.; Colantuoni, A.] Univ Naples Federico II, Sch Med, Dept Clin Med & Surg, Naples, Italy. [Cesarelli, M.; Romano, M.; Bifulco, P.] Univ Naples Federico II, Elect & TLC Engn, Dept Biomed, Naples, Italy. [D'Addio, G.] S Maugeri Fdn, Rehabil Inst Telese Telese Terme, Telese Terme, Italy. [Gorbach, A.] Natl Inst Hlth, Infrared Imaging Thermometry Unit, NIBIB, Bethesda, MD USA. RP Lapi, D (reprint author), Univ Naples Federico II, Sch Med, Dept Clin Med & Surg, Naples, Italy. EM antonio.colantuoni@unina.it RI D'Addio, Giovanni/B-5212-2015; OI D'Addio, Giovanni/0000-0001-6352-3077; Colantuoni, Antonio/0000-0003-1152-5630 NR 6 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-3969-5 PY 2014 BP 199 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BB5AO UT WOS:000343599700100 ER PT S AU Uhl, GR AF Uhl, George R. BE Uhl, GR TI Preface for Addiction Reviews SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Editorial Material; Book Chapter C1 NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1327 BP V EP V DI 10.1111/nyas.12563 D2 10.1111/nyas.12571 PG 1 WC Substance Abuse SC Substance Abuse GA BB5KA UT WOS:000343916500001 PM 25336391 ER PT S AU Gorelick, DA Zangen, A George, MS AF Gorelick, David A. Zangen, Abraham George, Mark S. BE Uhl, GR TI Transcranial magnetic stimulation in the treatment of substance addiction SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE addiction; substance use disorder; TMS; transcranial magnetic stimulation; treatment ID DORSOLATERAL PREFRONTAL CORTEX; COCAINE-DEPENDENT PATIENTS; TREATMENT-RESISTANT DEPRESSION; SHAM-CONTROLLED TRIALS; HF-RTMS SESSION; BRAIN-STIMULATION; MAJOR DEPRESSION; CORTICAL EXCITABILITY; DOPAMINE RELEASE; MOTOR CORTEX AB Transcranial magnetic stimulation (TMS) is a noninvasive method of brain stimulation used to treat a variety of neuropsychiatric disorders, but is still in the early stages of study as addiction treatment. We identified 19 human studies using repetitive TMS (rTMS) to manipulate drug craving or use, which exposed a total of 316 adults to active rTMS. Nine studies involved tobacco, six alcohol, three cocaine, and one methamphetamine. The majority of studies targeted high-frequency (5-20 Hz; expected to stimulate neuronal activity) rTMS pulses to the dorsolateral prefrontal cortex. Only five studies were controlled clinical trials: two of four nicotine trials found decreased cigarette smoking; the cocaine trial found decreased cocaine use. Many aspects of optimal treatment remain unknown, including rTMS parameters, duration of treatment, relationship to cue-induced craving, and concomitant treatment. The mechanisms of rTMS potential therapeutic action in treating addictions are poorly understood, but may involve increased dopamine and glutamate function in corticomesolimbic brain circuits and modulation of neural activity in brain circuits that mediate cognitive processes relevant to addiction, such as response inhibition, selective attention, and reactivity to drug-associated cues. rTMS treatment of addiction must be considered experimental at this time, but appears to have a promising future. C1 [Gorelick, David A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Zangen, Abraham] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Gorelick, DA (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, Tawes Bldg,POB 21247, Baltimore, MD 21228 USA. EM dgorelick@mprc.umaryland.edu FU Intramural NIH HHS [Z99 DA999999] NR 107 TC 26 Z9 27 U1 5 U2 16 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1327 BP 79 EP 93 DI 10.1111/nyas.12479 D2 10.1111/nyas.12571 PG 15 WC Substance Abuse SC Substance Abuse GA BB5KA UT WOS:000343916500006 PM 25069523 ER PT J AU Ren, Y Kitahara, CM de Gonzalez, AB Clero, E Brindel, P Maillard, S Cote, S Dewailly, E Rachedi, F Boissin, JL Sebbag, J Shan, L Bost-Bezeaud, F Petitdidier, P Xhaard, C Rubino, C de Vathaire, F AF Ren, Yan Kitahara, Cari Meinhold de Gonzalez, Amy Berrington Clero, Enora Brindel, Pauline Maillard, Stephane Cote, Suzanne Dewailly, Eric Rachedi, Frederique Boissin, Jean-Louis Sebbag, Joseph Shan, Larrys Bost-Bezeaud, Frederique Petitdidier, Patrick Xhaard, Constance Rubino, Carole de Vathaire, Florent TI Lack of Association between Fingernail Selenium and Thyroid Cancer Risk: A Case-Control Study in French Polynesia SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Thyroid cancer; selenium; diet; fingernail; case-control study ID PREDIAGNOSTIC SERUM SELENIUM; FISH CONSUMPTION; TRACE-ELEMENT; CARCINOMA; SUPPLEMENTATION; IODINE; POLYMORPHISMS; POPULATION; PREVENTION; BIOMARKERS AB Background: Numerous studies have suggested that selenium deficiency may be associated with an increased risk for several types of cancer, but few have focused on thyroid cancer. Materials and Methods: We examined the association between post-diagnostic fingernail selenium levels and differentiated thyroid cancer risk in a French Polynesian matched case-control study. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. Results: The median selenium concentration among controls was 0.76 mu g/g. Significantly, we found no association between fingernail selenium levels and thyroid cancer risk after conditioning on year of birth and sex and additionally adjusting for date of birth (highest versus lowest quartile: odds-ratio=1.12, 95% confidence interval: 0.66-1.90; p-trend=0.30). After additional adjustment for other covariates, this association remained non-significant (p-trend= 0.60). When restricting the analysis to thyroid cancer of 10 mm or more, selenium in nails was non-significantly positively linked to thyroid cancer risk (p-trend= 0.09). Although no significant interaction was evidenced between iodine in nails and selenium in nails effect (p=0.70), a non-significant (p-trend = 0.10) positive association between selenium and thyroid cancer risk was seen in patients with less than 3 ppm of iodine in nails. The highest fingernail selenium concentration in French Polynesia was in the Marquises Islands (M=0.87 mu g/g) and in the Tuamotu-Gambier Archipelago (M=0.86 mu g/g). Conclusions: Our results do not support, among individuals with sufficient levels of selenium, that greater long-term exposure to selenium may reduce thyroid cancer risk. Because these findings are based on post-diagnostic measures, studies with prediagnostic selenium are needed for corroboration. C1 [Ren, Yan; Clero, Enora; Brindel, Pauline; Maillard, Stephane; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] INSERM, UMR 1018, Radiat Epidemiol Grp, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France. [Ren, Yan; Clero, Enora; Brindel, Pauline; Maillard, Stephane; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] Inst Gustave Roussy, Villejuif, France. [Ren, Yan; Clero, Enora; Brindel, Pauline; Maillard, Stephane; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France. [Kitahara, Cari Meinhold; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Cote, Suzanne; Dewailly, Eric] CHU Quebec, Res Ctr, Area Populat Hlth & Optimal Hlth Practices, Quebec City, PQ, Canada. [Rachedi, Frederique; Bost-Bezeaud, Frederique] Terr Hosp Mamao, Papeete, Fr Polynesia. [Boissin, Jean-Louis] IPRAME, Papeete, Fr Polynesia. [Sebbag, Joseph] Paofai Clin, Papeete, Fr Polynesia. [Petitdidier, Patrick] Lab Boz, Papeete, Fr Polynesia. RP de Vathaire, F (reprint author), INSERM, UMR 1018, Radiat Epidemiol Grp, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France. EM Florent.DEVATHAIRE@gustaveroussy.fr RI Kitahara, Cari/R-8267-2016; de Vathaire, Florent/L-2983-2016 FU Association pour la Recherche contre le Cancer; Ligue Nationale Contre le Cancer; Direction Generale de la Sante; Comite de radioprotection de Electricite de France; Agence Francaise de Securite Sanitaire et Environnementale et du Travail; CHILD-THYR EEC programme; Fondation de France FX This study was supported by the Association pour la Recherche contre le Cancer, the Ligue Nationale Contre le Cancer, the Direction Generale de la Sante, the Comite de radioprotection de Electricite de France, Agence Francaise de Securite Sanitaire et Environnementale et du Travail, CHILD-THYR EEC programme and the Fondation de France. NR 42 TC 1 Z9 2 U1 0 U2 3 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2014 VL 15 IS 13 BP 5187 EP 5194 DI 10.7314/APJCP.2014.15.13.5187 PG 8 WC Oncology SC Oncology GA AR6WZ UT WOS:000343722900015 PM 25040973 ER PT J AU Kirshenbaum, AS Petrik, A Walsh, R Kirby, TL Vepa, S Wangsa, D Ried, T Metcalfe, DD AF Kirshenbaum, Arnold S. Petrik, Amy Walsh, Rosemary Kirby, Tara L. Vepa, Sury Wangsa, Danny Ried, Thomas Metcalfe, Dean D. TI A Ten-Year Retrospective Analysis of the Distribution, Use and Phenotypic Characteristics of the LAD2 Human Mast Cell Line SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Mast cell; Allergy; Material transfer; Fc epsilon R1; Stem cell factor; c-KIT ID RECEPTOR; PATIENT; GAMMA AB Background: In 2003, this laboratory published an account of the human mast cell line LAD2 (Laboratory of Allergic Diseases 2) that expressed Fc epsilon R1, responded to recombinant human stem cell factor (rhSCF) and resembled CD34+-derived human mast cells. LAD2 cells have now been distributed worldwide. To study the impact of this transfer, we analyzed the number of investigators receiving LAD2 cells and resulting publications. Methods: Records maintained in our laboratory, the Technology Transfer and Intellectual Property Office and Office of Technology Transfer, were reviewed for material transfer agreements (MTAs) and licensing agreements (LAs). Journals and impact factors were obtained from PubMed.gov by cross-referencing LAD2 and human mast cells from 2003 through November 2013. Results: Over 300 MTAs and 40 LAs were approved. LAD2 cells were shipped to over 30 countries. More than 80 papers have been published in journals with impact factors from 1.31 to 13.21. Intended uses include the study of receptors, degranulation, and cell signaling. LAD2 cells continue to express described markers and have consistent Fc epsilon R1-mediated degranulation. Conclusions: Success of the LAD2 line reflects the demand for a human mast cell line in research, the uniqueness of this cell line, and that it continues to exhibit minimal variation from its original description. We hope that the awareness of the impact of this cell line on mast cell research will encourage others to develop and distribute other similar cell lines with additional characteristics so as to address the limitations of depending on the study of cultured human mast cells from tissues. (C) 2014 S. Karger AG, Basel C1 [Kirshenbaum, Arnold S.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Petrik, Amy; Walsh, Rosemary] NIAID, Technol Transfer & Intellectual Property Off, Bethesda, MD 20892 USA. [Wangsa, Danny; Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA. [Kirby, Tara L.; Vepa, Sury] NIH, Off Technol Transfer, Rockville, MD USA. RP Kirshenbaum, AS (reprint author), NIAID, NIH, Lab Allerg Dis, Bldg 10,Room 11C210,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM Akirshenba@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 12 TC 4 Z9 4 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 EI 1423-0097 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2014 VL 164 IS 4 BP 265 EP 270 DI 10.1159/000365729 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AR5HB UT WOS:000343614500002 PM 25195635 ER PT J AU Dema, B Suzuki, R Rivera, J AF Dema, Barbara Suzuki, Ryo Rivera, Juan TI Rethinking the Role of Immunoglobulin E and Its High-Affinity Receptor: New Insights into Allergy and Beyond SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Editorial Material DE Antigen affinity; Autoimmunity; Basophils; Fc epsilon RI; Immunoglobulin E; Mast cells; Systemic lupus erythematosus ID FC-EPSILON-RI; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BASOPHILIC LEUKEMIA-CELLS; MAST-CELLS; IGE ANTIBODIES; DEFICIENT MICE; PLASMA-CELLS; GAMMA-RIIB; ACTIVATION; SURVIVAL AB Immunoglobulin E (IgE) and its high-affinity receptor (Fc epsilon RI) are well-known participants in the allergic response. The interaction of allergens with Fc epsilon RI-bound IgE antibodies is an essential step in mast cell/basophil activation and the subsequent release of allergic mediators. It is known that the affinity of the interaction between an IgE antibody and an allergen may differ, raising the question of whether Fc epsilon RI can decipher these differences. If so, do the cellular and physiological outcomes vary? Are the molecular mechanisms initiated by Fc epsilon RI similarly under low- or high-affinity interactions? Could the resulting inflammatory response differ? Recent discoveries summarized herein are beginning to shed new light on these important questions. What we have learned from them is that IgE and Fc epsilon RI form a complex regulatory network influencing the inflammatory response in allergy and beyond. (C) 2014 S. Karger AG, Basel C1 [Dema, Barbara; Suzuki, Ryo; Rivera, Juan] NIAMSD, Mol Immunol Sect, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov FU Intramural NIH HHS [ZIA AR041155-07, ZIA AR041156-07, ZIA AR041101-20] NR 59 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 EI 1423-0097 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2014 VL 164 IS 4 BP 271 EP 279 DI 10.1159/000365633 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AR5HB UT WOS:000343614500003 PM 25227903 ER PT J AU Bauler, TJ Chase, JC Wehrly, TD Bosio, CM AF Bauler, Timothy J. Chase, Jennifer C. Wehrly, Tara D. Bosio, Catharine M. TI Virulent Francisella tularensis Destabilize Host mRNA to Rapidly Suppress Inflammation SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE mRNA stability; Intracellular bacteria; Inflammation; Macrophage ID TNF-ALPHA; SCHU S4; INFECTION; MACROPHAGES; PROTEIN; CELLS; ESCAPE; INDUCTION; TULAREMIA; CYTOPLASM AB Highly virulent bacterial pathogens have evolved rapid means to suppress host inflammatory responses by unknown mechanisms. Here, we use virulent Francisella tularensis, the cause of lethal tularemia in humans, as a model to elucidate these mechanisms. We show that following infection of murine macrophages F. tularensis rapidly and selectively destabilizes mRNA containing adenylate-uridylate-rich elements that encode for cytokines and chemokines important in controlling bacterial infection. Degradation of host mRNA encoding interleukin (IL)-1 beta, IL-6 and CXCL1 did not require viable bacteria or de novo protein synthesis, but did require escape of intracellular organisms from endocytic vesicles into the host cytosol. The specific targeting of host mRNA encoding inflammatory cytokines and chemokines for decay by a bacterial pathogen has not been previously reported. Thus, our findings represent a novel strategy by which a highly virulent pathogen modulates host inflammatory responses critical to the evasion of innate immunity. (C) 2014 S. Karger AG, Basel C1 [Bauler, Timothy J.; Chase, Jennifer C.; Wehrly, Tara D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, RML,NIH, Hamilton, MT 59840 USA. EM bosioc@niaid.nih.gov RI Bosio, Catharine/D-7456-2015 FU Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX The authors also thank Dr. Jeffery Wilusz and Dr. Harlan Caldwell for helpful discussion and suggestions pertaining to this paper. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 39 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 6 BP 793 EP 805 DI 10.1159/000363243 PG 13 WC Immunology SC Immunology GA AR5SD UT WOS:000343642800008 PM 24902499 ER PT J AU Hijioka, M Ito, T Igarashi, H Ueda, K Fujiyama, T Lee, L Niina, Y Nakamura, T Jensen, RT Takayanagi, R AF Hijioka, M. Ito, T. Igarashi, H. Ueda, K. Fujiyama, T. Lee, L. Niina, Y. Nakamura, T. Jensen, R. T. Takayanagi, R. TI Chromogranin A is a Useful Marker in Japanese Patients with Pancreatic Neuroendocrine Tumors SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 05-07, 2014 CL Barcelona, SPAIN SP ENETS DE chromogranin a; pnet; japanese C1 [Hijioka, M.; Ito, T.; Igarashi, H.; Ueda, K.; Fujiyama, T.; Lee, L.; Niina, Y.; Takayanagi, R.] Kyushu Univ Hosp, Fukuoka 812, Japan. [Nakamura, T.; Jensen, R. T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2014 VL 99 IS 3-4 MA H8 BP 254 EP 254 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AR5RB UT WOS:000343640100098 ER PT J AU Saini, AK Nanda, JS Martin-Marcos, P Dong, JS Zhang, F Bhardwaj, M Lorsch, JR Hinnebusch, AG AF Saini, Adesh K. Nanda, Jagpreet S. Martin-Marcos, Pilar Dong, Jinsheng Zhang, Fan Bhardwaj, Monika Lorsch, Jon R. Hinnebusch, Alan G. TI Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating P-i release and conformational transitions of the preinitiation complex SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 40S RIBOSOMAL-SUBUNIT; GTP EXCHANGE FACTORS; SACCHAROMYCES-CEREVISIAE; MEDIATE BINDING; SITE SELECTION; PROTEIN; VIVO; EIF2B-EPSILON; COMMUNICATION; HYDROLYSIS AB eIF5 is the GTPase activating protein (GAP) for the eIF2 center dot GTP center dot Met-tRNA(i)(Met) ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2 center dot GDP center dot P-i. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of P-i release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R, G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui(-) mutations in numerous factors. We conclude that both of eIF5' s functions, regulating P-i release and stabilizing the closed PIC conformation, contribute to stringent AUG selection in vivo. C1 [Saini, Adesh K.; Martin-Marcos, Pilar; Dong, Jinsheng; Zhang, Fan; Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Saini, Adesh K.; Bhardwaj, Monika] Shoolini Univ Biotechnol & Management Sci, Dept Biotechnol, Solan 173229, Himachal Prades, India. [Nanda, Jagpreet S.; Lorsch, Jon R.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Mech & Regulat Prot Synth, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM sainiade@gmail.com; jon.lorsch@nih.gov; ahinnebusch@nih.gov RI university, shoolini/K-9336-2015; OI Lorsch, Jon/0000-0002-4521-4999 FU Intramural Program of the National Institutes of Health; National Institutes of Health Grant [GM62128]; Department of Science and Technology, Government of India Grant [Int/NZ/P-2/13]; National Institutes of Health [GM62128]; Department of Science and Technology, Government of India [Int/NZ/P-2/13] FX Intramural Program of the National Institutes of Health [in part to A.G.H. and J.R.L.]; National Institutes of Health Grant [GM62128] [formerly to J.R.L.]; Department of Science and Technology, Government of India Grant [Int/NZ/P-2/13] [to A.K.S.]. Funding for open access charge: Intramural Program of the National Institutes of Health [to A.G.H. and J.R.L.]; National Institutes of Health Grant [GM62128] [formerly to J.R.L.]; Department of Science and Technology, Government of India Grant [Int/NZ/P-2/13] [to A.K.S.]. NR 33 TC 6 Z9 6 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 15 BP 9623 EP 9640 DI 10.1093/nar/gku653 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AQ9ZO UT WOS:000343220300015 PM 25114053 ER PT J AU Abdelmohsen, K Panda, AC Kang, MJ Guo, R Kim, J Grammatikakis, I Yoon, JH Dudekula, DB Noh, JH Yang, XL Martindale, JL Gorospe, M AF Abdelmohsen, Kotb Panda, Amaresh C. Kang, Min-Ju Guo, Rong Kim, Jiyoung Grammatikakis, Ioannis Yoon, Je-Hyun Dudekula, Dawood B. Noh, Ji Heon Yang, Xiaoling Martindale, Jennifer L. Gorospe, Myriam TI NAR Breakthrough Article 7SL RNA represses p53 translation by competing with HuR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BINDING PROTEIN HUR; LONG NONCODING RNA; POSTTRANSCRIPTIONAL GENE-REGULATION; TARGET MESSENGER-RNAS; TUMOR SUPPRESSION; DNA-DAMAGE; EXPRESSION; PHOSPHORYLATION; GROWTH; CANCER AB Noncoding RNAs (ncRNAs) and RNA-binding proteins are potent post-transcriptional regulators of gene expression. The ncRNA 7SL is upregulated in cancer cells, but its impact upon the phenotype of cancer cells is unknown. Here, we present evidence that 7SL forms a partial hybrid with the 3' untranslated region (UTR) of TP53 mRNA, which encodes the tumor suppressor p53. The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes. Silencing 7SL led to increased binding of HuR to TP53 mRNA, an interaction that led to the promotion of p53 translation and increased p53 abundance. We propose that the competition between 7SL and HuR for binding to TP53 3' UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53. Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels. C1 [Abdelmohsen, Kotb; Panda, Amaresh C.; Kang, Min-Ju; Guo, Rong; Kim, Jiyoung; Grammatikakis, Ioannis; Yoon, Je-Hyun; Dudekula, Dawood B.; Noh, Ji Heon; Yang, Xiaoling; Martindale, Jennifer L.; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@mail.nih.gov; myriam-gorospe@nih.gov FU National Institute on Aging-Intramural Research Program [NIA-IRP], National Institutes of Health [NIH] FX National Institute on Aging-Intramural Research Program [NIA-IRP], National Institutes of Health [NIH]. NR 41 TC 26 Z9 27 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 15 BP 10099 EP 10111 DI 10.1093/nar/gku686 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AQ9ZO UT WOS:000343220300052 PM 25123665 ER PT S AU Sissung, TM Goey, AKL Ley, AM Strope, JD Figg, WD AF Sissung, Tristan M. Goey, Andrew K. L. Ley, Ariel M. Strope, Jonathan D. Figg, William D. BE Yan, Q TI Pharmacogenetics of Membrane Transporters: A Review of Current Approaches SO PHARMACOGENOMICS IN DRUG DISCOVERY AND DEVELOPMENT, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ABCB1; ABCG2; ABCC1; ABCC2; OATP1B1; OATP1B3; Transport; Polymorphisms ID SINGLE NUCLEOTIDE POLYMORPHISMS; MULTIDRUG-RESISTANCE GENE; HUMAN MDR1 GENE; BINDING CASSETTE TRANSPORTERS; TYROSINE KINASE INHIBITORS; NORMAL HUMAN-TISSUES; P-GLYCOPROTEIN MDR1; OATP1B1 OATP-C; ORGANIC ANION; DRUG TRANSPORTERS AB This chapter provides a review of the pharmacogenetics of membrane transporters, including ABC transporters and OATPs. Membrane transporters are heavily involved in drug disposition, by actively transporting substrate drugs between organs and tissues. As such, polymorphisms in the genes encoding these proteins may have a significant effect on the absorption, distribution, metabolism, excretion, and activity of compounds. Although few drug transporter polymorphisms have transitioned from the bench to the bedside, this chapter discusses clinical development of transporter pharmacogenetic markers. Finally, development of SLCO1B1 genotyping to avoid statin induced adverse drug reactions is discussed as a model case for transporter pharmacogenetics clinical development. C1 [Sissung, Tristan M.; Goey, Andrew K. L.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Ley, Ariel M.; Strope, Jonathan D.] NCI, Mol Pharmacol Program, Bethesda, MD 20892 USA. RP Sissung, TM (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 150 TC 3 Z9 3 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0956-8; 978-1-4939-0955-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1175 BP 91 EP 120 DI 10.1007/978-1-4939-0956-8_6 D2 10.1007/978-1-4939-0956-8 PG 30 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BB4NM UT WOS:000343242600007 PM 25150868 ER PT S AU Biragyn, A Lee-Chang, C Bodogai, M AF Biragyn, Arya Lee-Chang, Catalina Bodogai, Monica BE Vitale, G Mion, F TI Generation and Identification of Tumor-Evoked Regulatory B Cells SO REGULATORY B CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE tBregs; Tregs; Metastasis; 4T1 breast cancer; TARC-PE38 ID BREAST-CANCER METASTASIS; T-CELLS; RECEPTOR-ALPHA; MUTANT MICE; IMMUNITY; AUTOIMMUNITY; EXPRESSION; TIM-1 AB The involvement of Bregs in cancer remains poorly understood despite their well-documented regulation of responses to the self and protection from harmful autoimmunity. We recently discovered a unique regulatory B cell subset evoked by breast cancer to mediate protection of metastasizing cancer cells. These results together with the wealth of findings of the last 40 years on B cells in tumorigenesis suggest the existence of additional cancer Bregs modulating anticancer responses. To facilitate the search for them, here we provide our detailed protocol for the characterization and generation of tumor-evoked regulatory B cells. Wherever applicable, we also discuss nuances and uniqueness of a Breg study in cancer to warn potential pitfalls. C1 [Biragyn, Arya] NIA, Immunoregulat Sect, NIH, Baltimore, MD 21224 USA. [Biragyn, Arya] NIA, Lab Mol Biol & Immunol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Lee-Chang, Catalina; Bodogai, Monica] NIA, Immunoregulat Sect, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Biragyn, A (reprint author), NIA, Immunoregulat Sect, NIH, Baltimore, MD 21224 USA. RI Lee-Chang, Catalina/A-5580-2015 OI Lee-Chang, Catalina/0000-0002-7675-2124 FU Intramural NIH HHS [ZIA AG000443-06] NR 23 TC 3 Z9 5 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1161-5; 978-1-4939-1160-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1190 BP 271 EP 289 DI 10.1007/978-1-4939-1161-5_19 D2 10.1007/978-1-4939-1161-5 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4SN UT WOS:000343312900020 PM 25015287 ER PT J AU Scorza, FA Zarate, CA AF Scorza, Fulvio A. Zarate, Carlos A., Jr. TI Schizophrenia: if death occurs without warning, what we should propose for the near future? SO REVISTA DE PSIQUIATRIA CLINICA LA English DT Editorial Material ID SUDDEN CARDIAC DEATH; CARDIOVASCULAR-DISEASE; ANTIPSYCHOTIC-DRUGS; METABOLIC SYNDROME; POPULATION C1 [Scorza, Fulvio A.] Univ Fed Sao Paulo, EPM Unifesp, Escola Paulista Med, Disciplina Neurol Expt, Sao Paulo, Brazil. [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Scorza, FA (reprint author), Disciplina Neurol Expt, Rua Pedro Toledo 669,1 Andar, BR-04039032 Sao Paulo, Brazil. EM scorza.nexp@epm.br RI Scorza, Fulvio/C-7048-2013 OI Scorza, Fulvio/0000-0002-0694-8674 NR 26 TC 0 Z9 0 U1 1 U2 1 PU UNIV SAO PAULO, INST PSIQUIATRIA PI SAO PAULO PA RUA OVIDIO PIRES CAMPOS, 785, 1 ANDAR, SAO PAULO, 05403-010, BRAZIL SN 0101-6083 J9 REV PSIQ CLIN-BRAZIL JI Rev. Psiquiatr. Clin. PY 2014 VL 41 IS 4 BP 112 EP 113 DI 10.1590/0101-60830000000022 PG 2 WC Psychiatry SC Psychiatry GA AR6DS UT WOS:000343674200006 ER PT S AU Saleh, AD Cheng, H AF Saleh, Anthony D. Cheng, Hui BE Alvarez, ML Nourbakhsh, M TI Tapping MicroRNA Regulation Networks Through Integrated Analysis of MicroRNA-mRNA High-Throughput Profiles SO RNA MAPPING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE MicroRNA regulation; MicroRNA integrated analysis; MicroRNA expression profiling; MicroRNA statistical methods; MicroRNA correlation; The Cancer Genome Atlas (TCGA) microRNA analysis; MicroRNA target prediction; MicroRNA target prioritization ID EXPRESSION PROFILES; GENE-EXPRESSION; SEQ DATA; TARGET PREDICTION; HUMAN GENOME; CANCER; LET-7; DIFFERENTIATION; IDENTIFICATION; REPOSITORY AB Understanding the biological relevance and context of microRNA (miRNA) regulation of target mRNAs is difficult to ascertain because an individual miRNA aids simultaneously in the regulation of hundreds of mRNAs in a cell. With the increasing availability of large public datasets that profile both mRNA and miRNA expression levels from the same samples, it is possible to apply robust statistical methods to identify global negative correlations in miRNA and target mRNA expression. Using a dataset from The Cancer Genome Atlas as a case study, we show how to use linear regression analysis followed by permutation-based false discovery rate to assign high statistical power to pair-wise negative correlations of miRNA and mRNA expression. Used in conjunction with available prediction tools or other target databases, a high confidence dataset of global miRNA-mRNA interactions can be generated. We also describe further methods to prioritize identified interactions by integrating with mutation, copy number variation, methylation, or survival data to support observations and provide context. Finally, we discuss methods to experimentally validate selected novel targets. C1 [Saleh, Anthony D.; Cheng, Hui] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Saleh, AD (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NR 39 TC 0 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1062-5; 978-1-4939-1061-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1182 BP 279 EP 288 DI 10.1007/978-1-4939-1062-5_24 D2 10.1007/978-1-4939-1062-5 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4SK UT WOS:000343311200025 PM 25055919 ER PT J AU Glatz, M Muellegger, RR Hizo-Teufel, C Fingerle, V AF Glatz, Martin Muellegger, Robert R. Hizo-Teufel, Cecilia Fingerle, Volker TI Low prevalence of Borrelia bavariensis in Ixodes ricinus ticks in southeastern Austria SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Borrelia bavariensis; Ixodes ricinus; Ticks; Austria ID BURGDORFERI SENSU-LATO; SP-NOV; SPIELMANII; GERMANY; EUROPE AB Borrelia bavariensis was recently described as a distinct genospecies among the B. burgdorferi sensu lato complex. The prevalence of B. bavariensis in Austria, a highly endemic area for tick-transmitted pathogens, is scarcely characterized. To investigate the prevalence of B. bavariensis in Ixodes ricinus ticks we reevaluated the results of a study conducted in 518 ticks from southeastern Austria collected in 2002 and 2003. The presence of B. burgdorferi s.I.-specific DNA in ticks was analyzed by a PCR for the outer surface protein A (ospA) gene. Borrelia species were differentiated by restriction fragment length polymorphism (RFLP) analysis, and samples positive for B. bavariensis were further analyzed by multilocus sequence analysis. Two of 133 (1.5%) B. burgdorferi s.l.-positive I. ricinus ticks were infected with B. bavariensis. Both specimens were coinfected with the OspA serotype 5 of B. garinii. Borrelia bavariensis is present; however, seem to be rare in I. ricinus ticks in southeastern Austria. (C) 2014 Elsevier GmbH. All rights reserved. C1 [Glatz, Martin; Muellegger, Robert R.] Med Univ Graz, Dept Dermatol, Graz, Austria. [Glatz, Martin] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Muellegger, Robert R.] State Hosp Wiener Neustadt, Dept Dermatol, Wiener Neustadt, Austria. [Hizo-Teufel, Cecilia; Fingerle, Volker] German Natl Reference Ctr Borrelia, Bavarian Hlth & Food Safety Author, Oberschleissheim, Germany. RP Glatz, M (reprint author), NCI, Ctr Canc Res, Dermatol Branch, NIH, Bldg 10-12N260,10 Ctr Dr, Bethesda, MD 20892 USA. EM glatz.martin@gmx.net OI Fingerle, Volker/0000-0002-3835-5646 NR 11 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2014 VL 5 IS 6 BP 649 EP 650 DI 10.1016/j.ttbdis.2014.04.014 PG 2 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA AR2AG UT WOS:000343385100006 PM 25027234 ER PT S AU Lichten, M AF Lichten, Michael BE Smith, JS Burke, DJ TI Tetrad, Random Spore, and Molecular Analysis of Meiotic Segregation and Recombination SO YEAST GENETICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tetrad dissection; Meiosis; Recombination; Budding yeast; DNA preparation; Electrophoresis; Southern blotting ID SACCHAROMYCES-CEREVISIAE; CONVERSION; GENOME; YEAST AB The power of Saccharomyces cerevisiae as an experimental organism derives from its genetic tractability. Mutant variants can be isolated or constructed and phenotypically characterized with relative ease. In addition, the ability to recover and characterize all four products of meiosis, as haploid spores in a tetrad ascus, greatly facilitates determining the allelic composition of variants, measuring linkage relationships between alleles, and constructing new allele combinations for the analysis of genetic interactions. Saccharomyces cerevisiae also is a preeminent model organism for the study of meiotic recombination, by analysis of tetrads, by analysis of populations of single spores (often called random spore analysis), and by direct monitoring of recombination at the DNA level. This chapter contains methods for tetrad dissection, for random spore preparation, and for preparing DNA for molecular analysis from liquid cultures undergoing synchronous meiosis. C1 NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lichten, M (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 FU Intramural NIH HHS NR 10 TC 4 Z9 4 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1363-3; 978-1-4939-1362-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1205 BP 13 EP 28 DI 10.1007/978-1-4939-1363-3_2 D2 10.1007/978-1-4939-1363-3 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4NE UT WOS:000343239700003 PM 25213236 ER PT J AU Montenigro, PH Baugh, CM Daneshvar, DH Mez, J Budson, AE Au, R Katz, DI Cantu, RC Stern, RA AF Montenigro, Philip H. Baugh, Christine M. Daneshvar, Daniel H. Mez, Jesse Budson, Andrew E. Au, Rhoda Katz, Douglas I. Cantu, Robert C. Stern, Robert A. TI Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID FOOTBALL-LEAGUE PLAYER; BRAIN-INJURY; ALZHEIMERS-DISEASE; PUNCH DRUNK; HEAD-INJURY; IMPACT; CONCUSSION; SPECTRUM; SPORTS AB The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders. C1 [Montenigro, Philip H.; Stern, Robert A.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Baugh, Christine M.; Au, Rhoda; Katz, Douglas I.; Stern, Robert A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Daneshvar, Daniel H.] Boston Univ, Sch Med, Behav Neurosci Program, Boston, MA 02118 USA. [Mez, Jesse; Budson, Andrew E.; Stern, Robert A.] Boston Univ, Sch Med, BU Alzheimers Dis Ctr, Boston, MA 02118 USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Au, Rhoda] NHLBI, Framingham Heart Study, Boston, MA 02118 USA. [Katz, Douglas I.] Braintree Rehabil Hosp, Braintree, MA 02184 USA. [Cantu, Robert C.; Stern, Robert A.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA 01742 USA. RP Stern, RA (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 72 East Concord St, Boston, MA 02118 USA. EM bobstern@bu.edu OI Daneshvar, Daniel/0000-0003-3691-9513; Stern, Robert/0000-0002-5008-077X; Montenigro, Philip/0000-0003-4442-9207 FU National Institutes of Health (NIH) [R01 NS078337, P30 AG13846, U01NS086659, AG016495-11, NS17950, AG08122, AG029451, AG033040, AG033193, HL096917/, DARPA-BAA-11-65, R01 MH080295, R01 CA129769, U01 NS086659]; US Department of Defense [W81XWH-13-2-0064]; US Department of Veterans Affairs FX The authors wish to thank the following individuals for their contributions to this article: Nathan Fritts, Michael McClean, David Riley, Clifford Robbins, Daniel Seichepine, Julie Stamm, Yorghos Tripodis, and Florina Tynyanova. The preparation and writing of this article were supported, in part, through the following: National Institutes of Health (NIH) grants R01 NS078337 and P30 AG13846 and US Department of Defense grant W81XWH-13-2-0064. These funding agencies played no role in the writing of the manuscript or the decision to submit it. DHD and JM receive funding through NIH grant U01NS086659. AEB receives funding through NIH grant P30 AG13846 and the US Department of Veterans Affairs. RA receives funding through NIH grants AG016495-11, NS17950, AG08122, AG029451, AG033040, AG033193, HL096917/, and DARPA-BAA-11-65. RAS receives funding through NIH grants R01 NS078337, R01 MH080295, R01 CA129769, U01 NS086659, and P30 AG13846 and US Department of Defense grant W81XWH-13-2-0064. PHM, CMB, DIK, and RCC receive no external funding. NR 60 TC 28 Z9 28 U1 5 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 5 AR 68 DI 10.1186/s13195-014-0068-z PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TW UT WOS:000343200300013 PM 25580160 ER PT J AU Pich, EM Jeromin, A Frisoni, GB Hill, D Lockhart, A Schmidt, ME Turner, MR Mondello, S Potter, WZ AF Pich, Emilio Merlo Jeromin, Andreas Frisoni, Giovanni B. Hill, Derek Lockhart, Andrew Schmidt, Mark E. Turner, Martin R. Mondello, Stefania Potter, William Z. TI Imaging as a biomarker in drug discovery for Alzheimer's disease: is MRI a suitable technology? SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; CEREBRAL-BLOOD-FLOW; FUNCTIONAL CONNECTIVITY; CLINICAL-TRIALS; STRUCTURAL MRI; BRAIN; PET; DEMENTIA; PATTERNS; NEUROPATHOLOGY AB This review provides perspectives on the utility of magnetic resonance imaging (MRI) as a neuroimaging approach in the development of novel treatments for Alzheimer's disease. These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry. It was agreed that MRI, either structural or functional, could be used as a diagnostic, for assessing worsening of disease status, for monitoring vascular pathology, and for stratifying clinical trial populations. It was agreed also that MRI implementation is in its infancy, requiring more evidence of association with the disease states, test-retest data, better standardization across multiple clinical sites, and application in multimodal approaches which include other imaging technologies, such as positron emission tomography, electroencephalography, and magnetoencephalography. C1 [Pich, Emilio Merlo] F Hoffmann La Roche & Cie AG, Neurosci DTA pRED, Clin Imaging, CH-4070 Basel, Switzerland. [Jeromin, Andreas] Atlantic Biomarkers LLC, Gainesville, FL 32607 USA. [Frisoni, Giovanni B.] IRCCS San Giovanni di Dio Fatebenefratelli, Lab Epidemiol Neuroimaging & Telemed, I-25125 Brescia, Italy. [Hill, Derek] UCL, London, England. [Hill, Derek] IXICO Ltd, London EC1A 9PN, England. [Lockhart, Andrew] GlaxoSmithKline, Neurodegenerat DPU R&D China, Neurosci TA Unit, Clin Unit Cambridge,Addenbrookes Hosp, Cambridge CB2 2GG, England. [Schmidt, Mark E.] Janssen Pharmaceut NV, Neurosci Therapeut Area, Expt Med, B-2340 Beerse, Belgium. [Turner, Martin R.] Oxford Univ Nuffield, Dept Clin Neurosci, John Radcliffe Hosp, Oxford OX3 9DU, England. [Mondello, Stefania] Univ Messina, Dept Neurosci, I-98125 Messina, Italy. [Potter, William Z.] NIMH, Rockville, MD 20892 USA. RP Jeromin, A (reprint author), Atlantic Biomarkers LLC, 316 NW 28th Terrace, Gainesville, FL 32607 USA. EM andreasjeromin@gmail.com RI Schmidt, Mark/I-5052-2016; Frisoni, Giovanni B/K-1360-2016; OI Schmidt, Mark/0000-0003-3417-8977; Frisoni, Giovanni B/0000-0002-6419-1753; Mondello, Stefania/0000-0002-8587-3614; Turner, Martin/0000-0003-0267-3180 FU Wellcome Trust FX We thank the participants of the Wellcome Trust meeting on Brain Disorders for discussion, the Wellcome Trust for support, and Treasan Creavin and Lucy Criddle for their help in organizing this venue. NR 49 TC 4 Z9 4 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 4 AR 51 DI 10.1186/alzrt276 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TV UT WOS:000343200200013 ER PT B AU Giuliano, A Wells, S Reeve, T Abdullah, H Coventry, BJ AF Giuliano, Armando Wells, Samuel, Jr. Reeve, Thomas Abdullah, Hisham Coventry, Brendon J. BE Coventry, BJ TI Thyroid and Parathyroid Surgery SO BREAST, ENDOCRINE AND SURGICAL ONCOLOGY SE Surgery-Complications, Risks and Consequences LA English DT Article; Book Chapter ID MINIMALLY INVASIVE PARATHYROIDECTOMY; RECURRENT LARYNGEAL NERVE; VIDEO-ASSISTED THYROIDECTOMY; 13-YEAR PROSPECTIVE ANALYSIS; FOCUSED LATERAL APPROACH; LONG-TERM FUNCTIONALITY; CENTRAL NECK DISSECTION; PRIMARY HYPERPARATHYROIDISM; MULTINODULAR GOITER; SURGICAL-TREATMENT C1 [Giuliano, Armando] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. [Giuliano, Armando] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Giuliano, Armando] Cedars Sinai Med Ctr, Project Womens Guild, Los Angeles, CA 90048 USA. [Wells, Samuel, Jr.; Reeve, Thomas] NCI, Med Oncol Branch & Affiliates, NIH, Bethesda, MD 20892 USA. [Abdullah, Hisham] Putrajaya Hosp, Putrajaya, Malaysia. [Coventry, Brendon J.] Univ Adelaide, Royal Adelaide Hosp, Discipline Surg, Breast Endocrine & Surg Oncol Unit, Adelaide, SA 5000, Australia. RP Giuliano, A (reprint author), Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. NR 113 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-4471-5421-1; 978-1-4471-5420-4 J9 SURG COMPLI RISKS PY 2014 BP 67 EP 101 DI 10.1007/978-1-4471-5421-1_3 D2 10.1007/978-1-4471-5421-1 PG 35 WC Oncology; Surgery SC Oncology; Surgery GA BB3RY UT WOS:000343009900006 ER PT J AU Yufit, T Carson, P Falanga, V AF Yufit, Tatyana Carson, Polly Falanga, Vincent TI Topical Delivery of Cultured Stem Cells to Human Non-Healing Wounds: GMP Facility Development in an Academic Setting and FDA Requirements for an IND and Human Testing SO CURRENT DRUG DELIVERY LA English DT Article DE Food and Drug Administration (FDA); Good Manufacturing Practice (GMP); Investigational New Drug (IND); Mesenchymal Stem Cells (MSCs); Quality Assurance (QA); Quality Control (QC) ID FIBRIN AB With increasing emphasis on translational research, the need for appropriate regulatory oversight and approval has become essential. The requirements of the Food and Drug Administration (FDA) for Investigational New Drug (IND) exemption in studies that are investigator-initiated have become increasingly stringent. Moreover, academic institutions have not had substantial experience in establishing Good Manufacturing Practice (GMP) facilities required for manipulating human cells in vitro and for chemical or biochemical manufacturing. GMP regulations are established by the FDA under the authority of the Federal Food, Drug and Cosmetic Act. In this report, the authors outline the general strategy and some critical steps that an investigator and the institution may find helpful in developing a GMP facility, especially in an academic center. Also, more specifically and as proof of principle, we describe our approach to culturing autologous bone marrow-derived human mesenchymal stem cells (MSCs) and delivering them to non healing wounds. The lessons learned in this often lengthy and challenging process may be helpful to other academic institutions and investigators embarking on manipulating and delivering viable cells for human experimentation. C1 [Yufit, Tatyana; Carson, Polly; Falanga, Vincent] Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Providence, RI 02908 USA. [Yufit, Tatyana; Carson, Polly; Falanga, Vincent] Roger Williams Med Ctr, NIH, Ctr Biomed Res Excellence COBRE, Providence, RI 02908 USA. [Falanga, Vincent] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Falanga, Vincent] Tufts Univ, Dept Biochem, Boston, MA 02111 USA. RP Falanga, V (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, 50 Maude St, Providence, RI 02908 USA. EM vfalanga@bu.edu FU NIH, Center of Biomedical Research Excellence (COBRE) [NIGMS P20 GM103414]; Administrative and Regulatory COBRE Cores, Grant Award NIH/NIGMS [P20 GM103414]; NIH/NIAMS [R01AR060342]; Roger Williams Medical Center (RWMC) FX This work was supported by the following grants awarded to Dr. Vincent Falanga (as Principal Investigator) and Roger Williams Medical Center (RWMC) 1) the NIH, Center of Biomedical Research Excellence (COBRE), Grant Award # NIGMS P20 GM103414; 2) Administrative and Regulatory COBRE Cores, Grant Award NIH/NIGMS #P20 GM103414; 3) NIH/NIAMS Grant Award #R01AR060342. Recognition and special thanks go to Jennifer Brooks, MS, RAC, CQA and to David Fiore, BA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2018 EI 1875-5704 J9 CURR DRUG DELIV JI Curr. Drug Deliv. PY 2014 VL 11 IS 5 BP 572 EP 581 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ9HD UT WOS:000343159400004 PM 23517627 ER PT J AU Yuan, Y Adams, SD Dinauer, DM Rosenau, CM Uribe, MR Flegel, WA AF Yuan, Yao Adams, Sharon D. Dinauer, David M. Rosenau, Christopher M. Uribe, Marcela R. Flegel, Willy A. TI KIR MRNA EXPRESSION IN NATURAL KILLER CELLS AND PERIPHERAL BLOOD MONONUCLEAR CELLS ASSAYED BY QUANTITATIVE REAL-TIME PCR SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics (ASHI) CY OCT 20-24, 2014 CL Denver, CO SP Amer Soc Histocompatibil & Immunogenet C1 [Yuan, Yao; Adams, Sharon D.; Uribe, Marcela R.; Flegel, Willy A.] NIH, Bethesda, MD 20892 USA. [Dinauer, David M.; Rosenau, Christopher M.] Thermo Fisher Sci, Brown Deer, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PY 2014 VL 75 SU 1 MA P064 BP 96 EP 96 PG 1 WC Immunology SC Immunology GA AR1QM UT WOS:000343359700122 ER PT S AU Lalonde, F Gogtay, N Giedd, J Vydelingum, N Brown, D Tran, BQ Hsu, C Hsu, MK Cha, J Jenkins, J Ma, L Willey, J Wu, J Oh, K Landa, J Lin, CT Jung, TP Makeig, S Morabito, CF Moon, Q Yamakawa, T Lee, SY Lee, JH Szu, HH Cha, JH Kaur, B Byrd, K Dang, K Krzywicki, A Familoni, BO Larson, L Harkrider, S Krapels, KA Dai, LY AF Lalonde, Francois Gogtay, Nitin Giedd, Jay Vydelingum, Nadarajen Brown, David Tran, Binh Q. Hsu, Charles Hsu, Ming-Kai Cha, Jae Jenkins, Jeffrey Ma, Lien Willey, Jefferson Wu, Jerry Oh, Kenneth Landa, Joseph Lin, C. T. Jung, T. P. Makeig, Scott Morabito, Carlo Francesco Moon, Qyu Yamakawa, Takeshi Lee, Soo-Young Lee, Jong-Hwan Szu, Harold H. Cha, Jae Hoon Kaur, Balvinder Byrd, Kenneth Dang, Karen Krzywicki, Alan Familoni, Babajide O. Larson, Louis Harkrider, Susan Krapels, Keith A. Dai, Liyi BE Szu, HH Dai, L TI Brain Order Disorder 2nd Group Report of f-EEG SO INDEPENDENT COMPONENT ANALYSES, COMPRESSIVE SAMPLING, WAVELETS, NEURAL NET, BIOSYSTEMS, AND NANOENGINEERING XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Independent Component Analyses, Compressive Sampling, Wavelets, Neural Net, Biosystems, and Nanoengineering XII CY MAY 07-09, 2014 CL Baltimore, MD SP SPIE DE EEG; f -EEG; Power Spectral Density Law; Novelty Detection; Epileptics; Traumatic Brain Injury; Schizophrenia; Alzheimer ID SYNCHRONIZATION; TEMPERATURE; INTEGRATION AB Since the Brain Order Disorder (BOD) group reported on a high density Electroencephalogram (EEG) to capture the neuronal information using EEG to wirelessly interface with a Smartphone [1,2], a larger BOD group has been assembled, including the Obama BRAIN program, CUA Brain Computer Interface Lab and the UCSD Swartz Computational Neuroscience Center. We can implement the pair-electrodes correlation functions in order to operate in a real time daily environment, which is of the computation complexity of O(N-3) for N=10(2 similar to 3) known as functional f-EEG. The daily monitoring requires two areas of focus. Area #(1) to quantify the neuronal information flow under arbitrary daily stimuli-response sources. Approach to #1: (i) We have asserted that the sources contained in the EEG signals may be discovered by an unsupervised learning neural network called blind sources separation (BSS) of independent entropy components, based on the irreversible Boltzmann cellular thermodynamics(Delta S > 0), where the entropy is a degree of uniformity. What is the entropy? Loosely speaking, sand on the beach is more uniform at a higher entropy value than the rocks composing a mountain - the internal binding energy tells the paleontologists the existence of information. To a politician, landside voting results has only the winning information but more entropy, while a non-uniform voting distribution record has more information. For the human's effortless brain at constant temperature, we can solve the minimum of Helmholtz free energy (H = E - TS) by computing BSS, and then their pairwise-entropy source correlation function. (i) Although the entropy itself is not the information per se, but the concurrence of the entropy sources is the information flow as a functional-EEG, sketched in this 2nd BOD report. Area #(2) applying EEG bio-feedback will improve collective decision making (TBD). Approach to #2: We introduce a novel performance quality metrics, in terms of the throughput rate of faster (At) & more accurate (AA) decision making, which applies to individual, as well as team brain dynamics Following Nobel Laureate Daniel Kahnmen's novel "Thinking fast and slow", through the brainwave biofeedback we can first identify an individual's "anchored cognitive bias sources". This is done in order to remove the biases by means of individually tailored pre-processing. Then the training effectiveness can be maximized by the collective product Delta t * AA. For Area (sic)1, we compute a spatiotemporally windowed EEG in vitro average using adaptive time-window sampling The sampling rate depends on the type of neuronal responses, which is what we seek. The averaged traditional EEG measurements and are further improved by BSS decomposition into finer stimulus-response source mixing matrix [A] having finer & faster spatial grids with rapid temporal updates. Then, the functional EEG is the second order co-variance matrix defined as the electrode-pair fluctuation correlation function C((S) over tilde,(S) over tilde') of independent thermodynamic source components. (1) We define a 1-D Space filling curve as a spiral curve without origin. This pattern is historically known as the Peano-Hilbert arc length a. By taking the most significant bits of the Cartesian product a E O(x * y * z), it represents the arc length in the numerical size with values that map the 3-D neighborhood proximity into a 1-D neighborhood arc length representation. (2) 1-D Fourier coefficients spectrum have no spurious high frequency contents, which typically arise in lexicographical (zig-zag scanning) discontinuity [Hsu & Szu, "Peano-Hilbert curve," SPIE 20141. A simple Fourier spectrum histogram fits nicely with the Compressive Sensing CRDT Mathematics. (3) Stationary power spectral density is a reasonable approximation of EEG responses in striate layers in resonance feedback loops capable of producing a 100, 000 neuronal collective Impulse Response Function (IRT). The striate brain layer architecture represents an ensemble e.g. at V1-V4 of Brodmann areas 17-19 of the Cortex, i.e. stationary Wiener-Kintchine-Einstein Theorem. Goal 1: functional-EEG: After taking the 1-D space-filling curve, we compute the ensemble averaged 1-D Power Spectral Density (PSD) and then make use of the inverse FFT to generate f-EEG. (ii) Goal#2 individual wellness baseline (IWB): We need novel change detection, so we derive the ubiquitous fat-tail distributions for healthy brains PSD in outdoor environments (Signal=310 C; Noise=27 C: 5NR=310/300; 300 K=(1/40)eV). The departure from IWB might imply stress, fever, a sports injury, an unexpected fall, or numerous midnight excursions which may signal an onset of dementia in Home Alone Senior (HAS), discovered by telemedicine care-giver networks Aging global villagers need mental healthcare devices that are affordable, harmless, administrable (AHA) and user-friendly, situated in a clothing article such as a baseball hat and able to interface with pervasive Smartphones in daily environment. C1 [Lalonde, Francois; Gogtay, Nitin; Giedd, Jay; Vydelingum, Nadarajen; Brown, David; Tran, Binh Q.; Hsu, Charles; Hsu, Ming-Kai; Cha, Jae; Jenkins, Jeffrey; Ma, Lien; Willey, Jefferson; Wu, Jerry; Oh, Kenneth; Landa, Joseph; Lin, C. T.; Jung, T. P.; Makeig, Scott; Morabito, Carlo Francesco; Moon, Qyu; Yamakawa, Takeshi; Lee, Soo-Young; Lee, Jong-Hwan; Szu, Harold H.; Cha, Jae Hoon; Kaur, Balvinder; Byrd, Kenneth; Dang, Karen; Krzywicki, Alan; Familoni, Babajide O.; Larson, Louis; Harkrider, Susan; Krapels, Keith A.; Dai, Liyi] NIMH, NIH, Bethesda, MD 20892 USA. RP Lalonde, F (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-2002-8978; Familoni, Babajide/0000-0001-8381-6846 NR 17 TC 2 Z9 2 U1 1 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-055-6 J9 PROC SPIE PY 2014 VL 9118 DI 10.1117/12.2051706 PG 22 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BB4BK UT WOS:000343127000011 ER PT S AU Szu, H Hoekstra, P Landa, J Vydelingum, NA AF Szu, Harold Hoekstra, Philip Landa, Joseph Vydelingum, Nadarajen A. BE Szu, HH Dai, L TI Neo-Angiogenesis Metabolic Biomarker of Tumor-genesis Tracking By Infrared Joystick Contact Imaging in Personalized Homecare System SO INDEPENDENT COMPONENT ANALYSES, COMPRESSIVE SAMPLING, WAVELETS, NEURAL NET, BIOSYSTEMS, AND NANOENGINEERING XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Independent Component Analyses, Compressive Sampling, Wavelets, Neural Net, Biosystems, and Nanoengineering XII CY MAY 07-09, 2014 CL Baltimore, MD SP SPIE DE Neo-Angiogenesis; Metabolic Biomarker; Affordable Harmless Administrative Cancer Homecare AB We describe an affordable, harmless, and administrative (AHA) metabolic biomarker (MBM) for homecare cancer screening. It may save hundreds of thousands of women's and thousands of men's lives every year from breast cancer and melanoma. The goal is to increase the specificity of infrared (IR) imagery to reduce the false alarm rate (FAR). The patient's hands are immersed in icy cold water, about 11 C, for 30 seconds. We then compare two IR images, taken before and after the cold stimulus, and the difference reveals an enhanced signal and noise ratio (SNR) at tumorigenesis sites since the contraction of capillaries under cold challenge is natural to healthy capillaries, except those newly built capillaries during angiogenesis (Folkman, Nature 1995). Concomitant with the genome and the phenome (molecular signaling by phosphor-mediate protein causing inflammation by platelet activating factor (PAF) that transform cells from benign to malignant is the amplification of nitric oxide (NO) syntheses, a short-lived reactive oxygen species (ROS) that dilates regional blood vessels; superseding normal autonomic nervous system regulation. A rapidly growing tumor site might implicate accumulation of ROS, for which NO can rapidly stretch the capillary bed system usually having thinning muscular lining known as Neo-Angiogenesis (NA) that could behave like Leaky In-situ Faucet Effect (LIFE) in response to cold challenge. To emphasize the state of art knowledge of NA, we mentioned in passing the first generation of an anti-capillary growth drug, Avastin by Genetech; it is an antibody protein that is injected for metastasis, while the second generation drug; Sorafenib by Bayers (2001) and Sutent by Pfizer (2000) both target molecular signaling loci to block receptor associated tyrosine kinase induced protein phosphorylation in order to reverse the angiogenesis. Differentiating benign from malignant in a straightforward manner is required to achieve the wellness protocol, yet would become prohibitively expensive and impossible to follow through. For example, given the probability of detection (PD) about 0.1% over unspecified number of years (e.g. menopause years for breast cancer), one might need hundred thousand volunteers. We suggested a Time Reversal Invariant Paradigm (TRIP) (a private communication with Vatican) for gathering equivalent cancer symptom imagery from recovery histories of dozens of patients. We further mixed it with few % of recovered/non-sick cases for negative controls. Creating Virtual images and running videos of these, frame by frame, in two directions (forward and backward in time) resulted in identical Receiver Operation Characteristics (ROC) for both the computer Aided Target Recognition (AiTR) algorithm and the human radiological experts; namely PD versus FAR within the standard deviation; even though the physiology could be entirely different. Such a TRIP would be true taken by any memory-less instantaneous imagery devices (IR, ultrasound, X-rays, MRI excluding magnetic hysteresis memory). In summary, such an affordable, harmless, and administrative, neo-angiogenesis metabolic biomarker can help monitor the transitioning from benign to malignant states of high-risk home alone seniors and also monitor the progress of home alone seniors treatment at home. Therefore, Smartphone equipped with a day camera having IR spectral filtering for a contact self imaging called joystick, when augmented with ARA NA MBM, may be suited for HAS homecare. C1 [Szu, Harold] Catholic Univ Amer, Washington, DC 20064 USA. [Vydelingum, Nadarajen A.] Natl Canc Inst, Bethesda, MD USA. [Hoekstra, Philip] Thermal Scan Inc Birmingham, Birmingham, MI USA. [Landa, Joseph] BriarTek Inc Alexandria, Alexandria, VA USA. RP Szu, H (reprint author), Catholic Univ Amer, Washington, DC 20064 USA. RI Emchi, Karma/Q-1952-2016 NR 9 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-055-6 J9 PROC SPIE PY 2014 VL 9118 DI 10.1117/12.2049598 PG 13 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BB4BK UT WOS:000343127000019 ER PT J AU Pothayee, N Chen, DY Aronova, MA Qian, CQ Bouraoud, N Dodd, S Leapman, RD Koretsky, AP AF Pothayee, Nikorn Chen, Der-Yow Aronova, Maria A. Qian, Chunqi Bouraoud, Nadia Dodd, Stephen Leapman, Richard D. Koretsky, Alan P. TI Self-organized Mn2+-block copolymer complexes and their use for in vivo MR imaging of biological processes SO JOURNAL OF MATERIALS CHEMISTRY B LA English DT Article ID MANGANESE-ENHANCED MRI; BLOCK IONOMER COMPLEXES; CONTRAST AGENTS; OXIDE NANOPARTICLES; MNO NANOPARTICLES; POLYION COMPLEXES; BRAIN ACTIVATION; DRUG-DELIVERY; STABILITY; RELAXIVITY AB Manganese-block copolymer complexes (MnBCs) that contain paramagnetic Mn ions complexed with ionic-nonionic poly(ethylene oxide-b-poly(methacrylate) have been developed for use as a T-1-weighted MRI contrast agent. By encasing Mn ions within ionized polymer matrices, r1 values could be increased by 250-350% in comparison with free Mn ions at relatively high fields of 4.7 to 11.7 T. MnBCs were further manipulated by treatment with NaOH to achieve more stable complexes (iMnBCs). iMnBCs delayed release of Mn2+ which could be accelerated by low pH, indeed by cellular uptake via endocytosis into acidic compartments. Both complexes exhibited good T-1 contrast signal enhancement in the liver following intravenous infusion. The contrast was observed in the gallbladder due to the clearance of Mn ions from the liver to the biliary process. iMnBCs, notably, showed a delayed contrast enhancement profile in the gallbladder, which was interpreted to be due to degradation and excretion of Mn2+ ions into the gallbladder. Intracortical injection of iMnBCs into the rat brain also led to delayed neuronal transport to the thalamus. The delayed enhancement feature may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be internalized by endocytosis. C1 [Pothayee, Nikorn; Chen, Der-Yow; Qian, Chunqi; Bouraoud, Nadia; Dodd, Stephen; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Aronova, Maria A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM Koretskya@ninds.nih.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NINDS, NIH FX This research was supported by the Intramural Research Program at NINDS, NIH. The authors would like to thank Ms Kathryn Sharer for providing AML12 cell lines for uptake and cytotoxicity experiments. NR 49 TC 1 Z9 1 U1 3 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-750X EI 2050-7518 J9 J MATER CHEM B JI J. Mat. Chem. B PY 2014 VL 2 IS 40 BP 7055 EP 7064 DI 10.1039/c4tb00911h PG 10 WC Materials Science, Biomaterials SC Materials Science GA AQ7KR UT WOS:000342994100018 PM 25364506 ER PT J AU Shimazu, T Mirochnitchenko, O Phadtare, S Inouye, M AF Shimazu, Tsutomu Mirochnitchenko, Oleg Phadtare, Sangita Inouye, Masayori TI Regression of Solid Tumors by Induction of MazF, a Bacterial mRNA Endoribonuclease SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE MazF; Tumor regression; TA toxins ID ESCHERICHIA-COLI; ANTITUMOR RIBONUCLEASES; CYTOTOXIC RIBONUCLEASE; PROTEIN-SYNTHESIS; RANPIRNASE; CANCER; INHIBITION; ONCONASE AB MazF from Escherichia con is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. Its induction in mammalian cells has been shown to cause programmed cell death. Here we explored if a bacterial MazF-MazE toxin-antitoxin system can be used for gene therapy. For this, we first constructed a tetracycline-inducible MazF expression system in human embryonic kidney cells (T-Rex 293-mazF). Solid tumors were formed by injecting T-Rex 293-mazFcel Is into nude mice. All 8 mice injected with the cells developed solid tumors, which regressed upon induction of MazF. In 4 mice, tumors completely regressed, while in the remaining 4 mice, tumors reappeared after apparent significant regression, which was found to be due to the lack of presence of functional MazF. Notably, the MazF-mediated regression of the tumors was counteracted by the expression of its cognate antitoxin MazE. These results indicate that a bacterial MazF-MazE toxin-antitoxin system may have potential to be used as a therapeutic tool. (C) 2014 S. Karger AG, Basel C1 [Shimazu, Tsutomu; Inouye, Masayori] Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ USA. [Mirochnitchenko, Oleg] NIH, DCM ORIP Div Program Coordinat Planning & Strateg, Off Director, Bethesda, MD 20892 USA. [Phadtare, Sangita] Rowan Univ, Cooper Med Sch, Dept Biomed Sci, Camden, NJ 08103 USA. RP Phadtare, S (reprint author), Rowan Univ, Cooper Med Sch, Dept Biomed Sci, 401 S Broadway, Camden, NJ 08103 USA. EM phadtare@rowan.edu; inouye@cabm.rutgers.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 EI 1660-2412 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2014 VL 24 IS 4 BP 228 EP 233 DI 10.1159/000365509 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AR0OB UT WOS:000343270100003 PM 25196606 ER PT J AU Dale, RK Matzat, LH Lei, EP AF Dale, Ryan K. Matzat, Leah H. Lei, Elissa P. TI metaseq: a Python package for integrative genome-wide analysis reveals relationships between chromatin insulators and associated nuclear mRNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FORMAT; RUMPELSTILTSKIN; PROTEIN; ELEMENTS; DATASETS; BROWSER AB Here we introduce metaseq, a software library written in Python, which enables loading multiple genomic data formats into standard Python data structures and allows flexible, customized manipulation and visualization of data from high-throughput sequencing studies. We demonstrate its practical use by analyzing multiple datasets related to chromatin insulators, which are DNA-protein complexes proposed to organize the genome into distinct transcriptional domains. Recent studies in Drosophila and mammals have implicated RNA in the regulation of chromatin insulator activities. Moreover, the Drosophila RNA-binding protein Shep has been shown to antagonize gypsy insulator activity in a tissue-specific manner, but the precise role of RNA in this process remains unclear. Better understanding of chromatin insulator regulation requires integration of multiple datasets, including those from chromatin-binding, RNA-binding, and gene expression experiments. We use metaseq to integrate RIP-and ChIP-seq data for Shep and the core gypsy insulator protein Su(Hw) in two different cell types, along with publicly available ChIP-chip and RNA-seq data. Based on the metaseq-enabled analysis presented here, we propose a model where Shep associates with chromatin cotranscriptionally, then is recruited to insulator complexes in trans where it plays a negative role in insulator activity. C1 [Dale, Ryan K.; Matzat, Leah H.; Lei, Elissa P.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Dale, RK (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM dalerr@niddk.nih.gov; leielissa@niddk.nih.gov OI Dale, Ryan/0000-0003-2664-3744 FU Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases [DK015602-07] FX Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (DK015602-07 to E.L). NR 37 TC 5 Z9 5 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 14 BP 9158 EP 9170 DI 10.1093/nar/gku644 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AQ9ZH UT WOS:000343219200034 PM 25063299 ER PT J AU Schnettler, E Tykalova, H Watson, M Sharma, M Sterken, MG Obbard, DJ Lewis, SH McFarlane, M Bell-Sakyi, L Barry, G Weisheit, S Best, SM Kuhn, RJ Pijlman, GP Chase-Topping, ME Gould, EA Grubhoffer, L Fazakerley, JK Kohl, A AF Schnettler, Esther Tykalova, Hana Watson, Mick Sharma, Mayuri Sterken, Mark G. Obbard, Darren J. Lewis, Samuel H. McFarlane, Melanie Bell-Sakyi, Lesley Barry, Gerald Weisheit, Sabine Best, Sonja M. Kuhn, Richard J. Pijlman, Gorben P. Chase-Topping, Margo E. Gould, Ernest A. Grubhoffer, Libor Fazakerley, John K. Kohl, Alain TI Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FOREST-VIRUS REPLICON; INTERFERON ANTAGONIST; ARBOVIRUS INFECTION; IMMUNITY; REPLICATION; DROSOPHILA; IDENTIFICATION; ALPHAVIRUS; MOSQUITOS; ORIGIN AB Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class In-secta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi. C1 [Schnettler, Esther; McFarlane, Melanie; Kohl, Alain] MRC Univ Glasgow Ctr Virus Res, Glasgow G11 5JR, Lanark, Scotland. [Schnettler, Esther; Watson, Mick; Bell-Sakyi, Lesley; Barry, Gerald; Weisheit, Sabine; Fazakerley, John K.; Kohl, Alain] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland. [Schnettler, Esther; Watson, Mick; Bell-Sakyi, Lesley; Barry, Gerald; Weisheit, Sabine; Fazakerley, John K.; Kohl, Alain] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush EH25 9RG, Midlothian, Scotland. [Tykalova, Hana; Grubhoffer, Libor] Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Budweis, Czech Republic. [Tykalova, Hana; Grubhoffer, Libor] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Ceske Budejovice 37005, Budweis, Czech Republic. [Sharma, Mayuri; Kuhn, Richard J.] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. [Sterken, Mark G.; Pijlman, Gorben P.] Wageningen Univ, Lab Virol, NL-6708 PB Wageningen, Netherlands. [Obbard, Darren J.; Lewis, Samuel H.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland. [Obbard, Darren J.; Lewis, Samuel H.] Univ Edinburgh, Ctr Infect Immun & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland. [Best, Sonja M.] NIAID, Innate Immun & Pathogenesis Unit, Virol Lab, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Chase-Topping, Margo E.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland. [Gould, Ernest A.] Fac Med Timone, Unite Virus Emergents, F-13385 Marseille 05, France. [Gould, Ernest A.] Ctr Hydrol & Ecol, Wallingford OX10 8BB, Oxon, England. RP Kohl, A (reprint author), MRC Univ Glasgow Ctr Virus Res, Glasgow G11 5JR, Lanark, Scotland. EM Esther.Schnettler@glasgow.ac.uk; alain.kohl@glasgow.ac.uk RI Obbard, Darren/A-9235-2008; Grubhoffer, Libor/G-9762-2014; OI Obbard, Darren/0000-0001-5392-8142; Lewis, Samuel H/0000-0001-8967-6661; Watson, Mick/0000-0003-4211-0358; Pijlman, Gorben/0000-0001-9301-0408; Sterken, Mark/0000-0001-7119-6213; Fazakerley, John/0000-0001-7071-105X FU Netherlands Organisation for Scientific Research NWO [Rubicon fellowship] [825.10.021]; UK Biotechnology and Biological Sciences Research Council [Roslin Institute Strategic Programme Grant]; UK Medical Research Council; Wellcome Trust [Biomedical Resources Grant] [088588, RCDF 085064/Z/08/Z]; FP7-PEOPLE-ITN programme [EU Grant] [238511 POSTICK ITN]; Czech Science Foundation (GACR) [P302/12/2490]; National Institutes of Health [AIO055672]; Division of Intramural Research, National Institutes of Health, National Institute of Allergy and Infectious Diseases FX Netherlands Organisation for Scientific Research NWO [Rubicon fellowship, 825.10.021 to E. S.]; UK Biotechnology and Biological Sciences Research Council [Roslin Institute Strategic Programme Grant to J.K.F. and A. K.]; UK Medical Research Council [to A. K. and E. S.]; Wellcome Trust [Biomedical Resources Grant 088588 to J.K.F. and L. B. S., RCDF 085064/Z/08/Z to D.O.]; FP7-PEOPLE-ITN programme [EU Grant No. 238511 POSTICK ITN to S. W.]; Czech Science Foundation (GACR) [P302/12/2490 to H. T.], National Institutes of Health [AIO055672 to R.J.K.]; Division of Intramural Research, National Institutes of Health, National Institute of Allergy and Infectious Diseases [to S. M. B.]. Funding for open access charge: UK Medical Research Council. NR 65 TC 24 Z9 25 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 14 BP 9436 EP 9446 DI 10.1093/nar/gku657 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AQ9ZH UT WOS:000343219200056 PM 25053841 ER PT J AU Pongpiachan, S AF Pongpiachan, Siwatt TI Application of Binary Diagnostic Ratios of Polycyclic Aromatic Hydrocarbons for Identification of Tsunami 2004 Backwash Sediments in Khao Lak, Thailand SO SCIENTIFIC WORLD JOURNAL LA English DT Article ID INDIAN-OCEAN-TSUNAMI; COASTAL MARINE-SEDIMENTS; INNER CONTINENTAL-SHELF; FRASER-RIVER BASIN; LUNG-CANCER RISK; BOUND PAHS; VERTICAL-DISTRIBUTION; SOURCE APPORTIONMENT; MEDITERRANEAN SEA; SURFACE SEDIMENTS AB Identification of Tsunami deposits has long been a controversial issue among geologists. Although there are many identification criteria based on the sedimentary characteristics of unequivocal Tsunami deposits, the concept still remains ambiguous. Apart from relying on some conventional geological, sedimentological, and geoscientific records, geologists need some alternative "proxies" to identify the existence of Tsunami backwash in core sediments. Polycyclic aromatic hydrocarbons (PAHs) are a class of very stable organic molecules, which can usually be presented as complex mixtures of several hundred congeners; one can assume that the "Tsunami backwash deposits" possess different fingerprints of PAHs apart from those of "typical marine sediments." In this study, three-dimensional plots of PAH binary ratios successfully identify the Tsunami backwash deposits in comparison with those of global marine sediments. The applications of binary ratios of PAHs coupled with HCA are the basis for developing site-specific Tsunami deposit identification criteria that can be applied in paleotsunami deposits investigations. C1 NIDA, Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand. RP Pongpiachan, S (reprint author), NIDA, Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, 118 Moo3,Sereethai Rd, Bangkok 10240, Thailand. EM pongpiajun@gmail.com FU National Research Council of Thailand (NRCT) FX This work was performed with the approval of National Institute of Development Administration (NIDA) and financial support from National Research Council of Thailand (NRCT). The author acknowledges Assistant Professor Dr. Charnwit Kositanont, Assistant Professor Dr. Surat Bualert, and Ms. Teeta Intasaen from Inter-Department of Environmental Science, Faculty of Graduate Studies, Chulalongkorn University, for their contributions to filed samplings and laboratory works. The author would like to express his deepest gratitude to Ms. Woranuch Deelaman, Ms. Jitlada Muprasit, Dr. Peter Feldens, and Dr. Klaus Schwarzer for their kind assistance. NR 70 TC 2 Z9 2 U1 1 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2014 AR 485068 DI 10.1155/2014/485068 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AR3WP UT WOS:000343519800001 ER PT J AU Cloninger, A Czaja, W Bai, RL Basser, PJ AF Cloninger, Alexander Czaja, Wojciech Bai, Ruiliang Basser, Peter J. TI Solving 2D Fredholm Integral from Incomplete Measurements Using Compressive Sensing SO SIAM JOURNAL ON IMAGING SCIENCES LA English DT Article DE Fredholm integral; nuclear magnetic resonance; compressive sensing; matrix completion; tight frame ID LOW-RANK MATRICES; THRESHOLDING ALGORITHM; MAGNETIZATION-TRANSFER; MULTIDIMENSIONAL NMR; MULTICOMPONENT T-1; STEADY-STATE; COMPLETION; RELAXATION; SPECTROSCOPY; INFORMATION AB We present an algorithm to solve the two-dimensional Fredholm integral of the first kind with tensor product structure from a limited number of measurements, with the goal of using this method to speed up nuclear magnetic resonance spectroscopy. This is done by incorporating compressive sensing-type arguments to fill in missing measurements, using a priori knowledge of the structure of the data. In the first step we recover a compressed data matrix from measurements that form a tight frame, and establish that these measurements satisfy the restricted isometry property. Recovery can be done from as few as 10% of the total measurements. In the second and third steps, we solve the zeroth-order regularization minimization problem using the Venkataramanan-Song-Hurlimann algorithm. We demonstrate the performance of this algorithm on simulated data and show that our approach is a realistic approach to speeding up the data acquisition. C1 [Cloninger, Alexander; Czaja, Wojciech] Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA. [Bai, Ruiliang] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [Bai, Ruiliang; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. RP Cloninger, A (reprint author), Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA. EM alex@math.umd.edu; wojtek@math.umd.edu; ruiliang.bai@nih.gov; pjbasser@helix.nih.gov NR 57 TC 4 Z9 4 U1 3 U2 8 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1936-4954 J9 SIAM J IMAGING SCI JI SIAM J. Imaging Sci. PY 2014 VL 7 IS 3 BP 1775 EP 1798 DI 10.1137/130932168 PG 24 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Mathematics, Applied; Imaging Science & Photographic Technology SC Computer Science; Mathematics; Imaging Science & Photographic Technology GA AR0BJ UT WOS:000343228200012 ER PT J AU Sankineni, S Osman, M Choyke, PL AF Sankineni, Sandeep Osman, Murat Choyke, Peter L. TI Functional MRI in Prostate Cancer Detection SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID DIFFUSION-WEIGHTED MRI; SEMINAL-VESICLE INVASION; MULTIPARAMETRIC MRI; ENDORECTAL COIL; 3 T; RADICAL PROSTATECTOMY; PERIPHERAL ZONES; GLEASON SCORE; B VALUE; LESIONS AB Multiparametric magnetic resonance imaging (MP-MRI) has emerged as a promising method for the detection of prostate cancer. The functional MRI components of the MP-MRI consist of the diffusion weighted MRI, dynamic contrast enhanced MRI, and magnetic resonance spectroscopic imaging. The purpose of this paper is to review the existing literature about the use of functional MRI in prostate cancer detection. C1 [Sankineni, Sandeep; Osman, Murat; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov NR 53 TC 1 Z9 2 U1 2 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 590638 DI 10.1155/2014/590638 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AQ6RO UT WOS:000342941700001 ER PT J AU Xiong, JH AF Xiong, Jianhua TI SALL4: Engine of Cell Stemness SO CURRENT GENE THERAPY LA English DT Article DE Cancer; Duane syndrome; embryonic development; hematopoiesis; Sall4; stem cell ID YOLK-SAC TUMORS; EARLY EMBRYONIC-DEVELOPMENT; TRANSCRIPTION FACTOR SALL4; ACUTE MYELOID-LEUKEMIA; RENAL-OCULAR SYNDROME; HOMEOTIC GENE SPALT; ZINC-FINGER PROTEIN; RADIAL RAY SYNDROME; HOLT-ORAM-SYNDROME; GERM-CELL AB The spalt (sal) family is a class of evolutionarily conserved genes originally identified in Drosophila as homeotic genes required for embryonic development. In vertebrates, the expression of sal-like 4 (SALL4) is specifically enriched in both embryonic and adult stem/stem-like cells. SALL4 is a master regulator that contributes to cell stemness in biological development and tumor growth. Thus, Sall4 has emerged as a target for gene therapy. In addition, numerous mutations affecting the Sall4 gene have been discovered and clinically linked to a series of congenital abnormalities, such as Duane/Duane-related syndromes, ventricular septal defect and premature ovarian failure. This review delineates the underlying mechanisms of key functions of SALL4 and its use as a target for gene therapy. Finally, I summarize and discuss advances made on the application of Sall4 and its functions in diagnostics and treatments for human diseases. C1 [Xiong, Jianhua] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Xiong, JH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM jianhua.xiong@nih.gov RI Xiong, Jianhua/D-6099-2015 OI Xiong, Jianhua/0000-0002-2740-4027 NR 138 TC 3 Z9 3 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 EI 1875-5631 J9 CURR GENE THER JI Curr. Gene Ther. PY 2014 VL 14 IS 5 BP 400 EP 411 DI 10.2174/1566523214666140825125138 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AQ8WV UT WOS:000343120300007 PM 25174577 ER PT S AU Beare, PA Heinzen, RA AF Beare, Paul A. Heinzen, Robert A. BE Vergunst, AC OCallaghan, D TI Gene Inactivation in Coxiella burnetii SO HOST-BACTERIA INTERACTIONS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Coxiella burnetii; Electroporation; Genetic transformation; Targeted gene inactivation; Axenic media; Transposon; Counterselection; Homologous recombination ID Q-FEVER; APOPTOSIS; SECRETION; MACROPHAGES; SYSTEMS; PROTEIN; GROWTH AB Coxiella burnetii, the agent of human Q fever, is a zoonotic bacterial pathogen with a worldwide distribution. Owing to an historic lack of methods for genetic manipulation, virulence factors deployed by this bacterium for disease pathogenesis are poorly understood. However, the recent advance of host cell-free (axenic) growth of C. burnetii has coincided with development of several new genetic technologies including site-specific and random transposon systems, shuttle vectors, and an inducible gene expression system. We have recently added two methods for targeted gene inactivation to the expanding C. burnetii genetics toolbox. Here, we describe a "loop in/loop out" gene inactivation system for C. burnetii. This procedure allows for generation of site-directed mutants in approximately 10 weeks and has been used by our laboratory to generate more than 50 individual C. burnetii mutants. The collection of C. burnetii genetic tools now allows for conventional mutation and complementation strategies to define virulence factors. C1 [Beare, Paul A.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Beare, PA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. FU Intramural NIH HHS NR 19 TC 4 Z9 4 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1261-2; 978-1-4939-1260-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1197 BP 329 EP 345 DI 10.1007/978-1-4939-1261-2_19 D2 10.1007/978-1-4939-1261-2 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology; Infectious Diseases SC Biochemistry & Molecular Biology; Immunology; Infectious Diseases GA BB3MY UT WOS:000342900400020 PM 25172290 ER PT J AU Kido, T Yoneda, M Cai, Y Matsubara, T Ward, JM Kimura, S AF Kido, Taketomo Yoneda, Mitsuhiro Cai, Yan Matsubara, Tsutomu Ward, Jerrold M. Kimura, Shioko TI Secretoglobin Superfamily Protein SCGB3A2 Deficiency Potentiates Ovalbumin-Induced Allergic Pulmonary Inflammation SO MEDIATORS OF INFLAMMATION LA English DT Article ID UTEROGLOBIN-RELATED PROTEIN-1; EMBRYONIC STEM-CELLS; BINDING-PROTEIN; AIRWAY INFLAMMATION; MOUSE; LUNG; EXPRESSION; DISEASE; GENE; MICE AB Secretoglobin (SCGB) 3A2, a cytokine-like secretory protein of small molecular weight, which may play a role in lung inflammation, is predominantly expressed in airway epithelial cells. In order to understand the physiological role of SCGB3A2, Scgb3a2(-/-) mice were generated and characterized. Scgb3a2(-/-) mice did not exhibit any overt phenotypes. In ovalbumin- (OVA-) induced airway allergy inflammation model, Scgb3a2(-/-) mice in mixed background showed a decreased OVA-induced airway inflammation, while six times C57BL/6NCr backcrossed congenic Scgb3a2(-/-) mice showed a slight exacerbation of OVA-induced airway inflammation as compared to wild-type littermates. These results indicate that the loss of SCGB3A2 function was influenced by amodifier gene(s) in mixed genetic background and suggest that SCGB3A2 has anti-inflammatory property. The results further suggest the possible use of recombinant human SCGB3A2 as an anti-inflammatory agent. C1 [Kido, Taketomo; Yoneda, Mitsuhiro; Cai, Yan; Matsubara, Tsutomu; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Kido, Taketomo] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan. [Matsubara, Tsutomu] Osaka City Univ, Grad Sch Med, Dept Anat, Osaka 5458585, Japan. [Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD 20866 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov RI Cai, Yan/P-4383-2015; OI Kimura, Shioko/0000-0001-9627-6818 FU National Cancer Institute, Center for Cancer Research, and Intramural Research Program FX This study was supported by the National Cancer Institute, Center for Cancer Research, and Intramural Research Program. NR 25 TC 0 Z9 0 U1 1 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2014 AR 216465 DI 10.1155/2014/216465 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AQ6RN UT WOS:000342941600001 ER PT J AU Sechi, G Bedognetti, D Sgarrella, F Van Eperen, L Marincola, FM Bianco, A Delogu, LG AF Sechi, Giovanni Bedognetti, Davide Sgarrella, Francesco Van Eperen, Laura Marincola, Francesco M. Bianco, Alberto Delogu, Lucia Gemma TI The perception of nanotechnology and nanomedicine: a worldwide social media study SO NANOMEDICINE LA English DT Article DE carbon nanotubes; Facebook; graphene; nanomedicine; nanotechnology; public opinions; social network ID FUNCTIONALIZED CARBON NANOTUBES; RISK PERCEPTIONS; UNITED-STATES; PUBLIC-ATTITUDES; ENGAGEMENT; FACEBOOK; EUROPE; FUTURE; AGENTS; CELLS AB We explore at a world level the awareness of nanotechnology expressed through the most popular online social media: Facebook. We aimed at identifying future trends, the most interested countries and the public perception of ethics, funding and economic issues. We found that graphene and carbon nanotubes are the most followed nanomaterials. Our poll showed that the continents with the most interest are Asia and Africa. A total of 43% would like to have a world commission regulating nanomedicine. In addition, 43% would give priority to theranostics. Over 90% believe that nanomedicine has an economic impact. Finally, we observed that the continents of living and origin of poll contributors correlated with ethic and funding opinions. This study highlights the potential of online social media to influence scientific communities, grant committees and nanotechnology companies, spreading nanotechnology awareness in emerging countries and among new generations. C1 [Sechi, Giovanni] Univ Sassari, Dipartimento Sci Polit Sci Comunicaz & Ingn Infor, I-07100 Sassari, Italy. [Sechi, Giovanni] Ecole Normale Super Lyon, UMR Triangle Lyon 5206, Lyon, France. [Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Bedognetti, Davide; Marincola, Francesco M.] NIH, Trans Natl Inst Hlth, Ctr Human Immunol, Bethesda, MD 20892 USA. [Bedognetti, Davide; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Sgarrella, Francesco; Delogu, Lucia Gemma] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy. [Van Eperen, Laura] Van Eperen & Co, Rockville, MD 20850 USA. [Bianco, Alberto] CNRS, Inst Biol Mol & Cellulaire, Lab Immunopathol & Chim Therapeut, F-67000 Strasbourg, France. RP Delogu, LG (reprint author), Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy. EM lgdelogu@uniss.it OI Bedognetti, Davide/0000-0002-5857-773X FU Fondazione Banco di Sardegna [186/2011.0484, 2013.1308]; University of Sassari (Italy); Sardinia Region [CRP-59720]; Gianfranco del Prete, doctor and scientist: The future: medicine, biology and nanotechnology Award; European Community [604391]; [U.E. POR 2007-2013] FX The authors are grateful to G Razzu for technical help recording data. The authors wish to thank A Carta and S Ennas of the patent office Technology Park Sardinia for technical help. G Sechi wishes to thank C Tidore for support and the financial contribution of U.E. POR 2007-2013. This work was partly supported by the Fondazione Banco di Sardegna (grant no. 186/2011.0484, 2013.1308 To LG Delogu), the University of Sassari (Italy), the Sardinia Region (grant no. CRP-59720 to LA Delogu) and the "Gianfranco del Prete, doctor and scientist: The future: medicine, biology and nanotechnology Award" to LG Delogu. A Bianco wishes to thank the European Community program FP7-ICT-2013-FET-F (GRAPHENE, n. 604391). LG Delogu wishes to thank Sardinia Region for supporting an Invited Professorship to A Bianco. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 61 TC 13 Z9 13 U1 7 U2 30 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2014 VL 9 IS 10 BP 1475 EP 1486 DI 10.2217/NNM.14.78 PG 12 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AQ7EV UT WOS:000342976300010 PM 25253496 ER PT J AU Xu, XW Zhang, K Zhao, L Wang, DD Bu, WH Zheng, CY Sun, HC AF Xu, Xiaowei Zhang, Kai Zhao, Liang Wang, Dandan Bu, Wenhuan Zheng, Changyu Sun, Hongchen TI Characteristics of three sizes of silica nanoparticles in the osteoblastic cell line, MC3T3-E1 SO RSC ADVANCES LA English DT Article ID IN-VIVO; CANCER-THERAPY; DIAGNOSIS; PROLIFERATION AB Reconstruction of bone defects is still challenging for the clinician, owing to the little achievement in the effect of bone materials on osteoblastic cells. In this work, the size effect of silica nanoparticles (SNs) on cellular uptake, cytotoxicity, and cell function in the osteoblast cell line, MC3T3-E1, is studied to reveal the potentials of SNs for bone regeneration. The SNs with three different sizes are prepared using the Stober approach and labeled with FITC. Confocal laser scanning microscopy, fluorescence-activated cell sorting and fluorescence spectrophotometry are used to evaluate the effects. All three different sized FITC-labeled silica nanoparticles have similar cellular uptake (>90%), determined by fluorescence-activated cell sorting (FACS) analysis, which suggest that all three silica nanoparticles generally have good cellular affinity. Fluorescence spectrophotometry results, however, indicate that cellular uptake is increased with a decrease in the size of the SN. Interestingly, the smaller silica nanoparticles could induce more MC3T3-E1 cell apoptosis than that of larger silica nanoparticles, and it is dose-dependent. MTT assays demonstrated that all three SNs are capable to decrease cell proliferation at a higher concentration (100 mu g ml(-1)). These results indicate that the SNs are cytotoxic, which is size and concentration-dependent. Importantly, all three SNs can directly stimulate mineralized nodule formation, which is also size-dependent. These results suggest that SNs are potentially applicable in bone regeneration, and it is possible to decrease unwanted side effects by controlling dose and size of SNs. C1 [Xu, Xiaowei; Zhao, Liang; Wang, Dandan; Bu, Wenhuan; Sun, Hongchen] Jilin Univ, Coll & Hosp Stomatol, Dept Oral Pathol, Changchun 130021, Peoples R China. [Zhang, Kai] Jilin Univ, Coll Chem, State Key Lab Supramol Struct & Mat, Changchun 130012, Peoples R China. [Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Sun, HC (reprint author), Jilin Univ, Coll & Hosp Stomatol, Dept Oral Pathol, Changchun 130021, Peoples R China. EM hcsun@jlu.edu.cn FU National Natural Science Foundation of China [81320108011, 81271111, 30830108]; Science Technology Program of Jilin Province [2011I051, 200705350, 201201064]; Jilin University [2014068, 20121128] FX This study was supported by grants from the National Natural Science Foundation of China (81320108011, 81271111, 30830108), the Science Technology Program of Jilin Province (2011I051, 200705350, 201201064) and the Graduate Innovation Fund of Jilin University (2014068, 20121128). NR 37 TC 1 Z9 1 U1 5 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 87 BP 46481 EP 46487 DI 10.1039/c4ra06863g PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA AQ4JJ UT WOS:000342761800010 ER PT S AU Kidder, BL Zhao, KJ AF Kidder, Benjamin L. Zhao, Keji BE Kidder, BL TI Efficient Library Preparation for Next-Generation Sequencing Analysis of Genome-Wide Epigenetic and Transcriptional Landscapes in Embryonic Stem Cells SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Next-generation sequencing; Library construction; Chromatin immunoprecipitation; ChIP-Seq; RNA-Seq; Gene expression; Transcriptome; Embryonic stem cells ID SELF-RENEWAL; PLURIPOTENCY; NETWORK; GENES; STATE AB Gene expression in embryonic stem (ES) cells is regulated in part by a network of transcription factors, epigenetic regulators, and histone modifications that influence the underlying chromatin in a way that is conducive or repressive for transcription. Advances in next-generation sequencing technology have allowed for the genome-wide analysis of chromatin constituents and protein-DNA interactions at high resolution in ES cells and other stem cells. While many studies have surveyed genome-wide profiles of a few factors and expression changes at a fixed time point in undifferentiated ES cells, few have utilized an integrative approach to simultaneously survey protein-DNA interactions, histone modifications, and expression programs during ES cell self-renewal and differentiation. To identify transcriptional networks that regulate pluripotency and differentiation, it is important to generate high-quality genome-wide maps of transcription factors, chromatin factors, and histone modifications and to survey global gene expression profiles. Here, to interrogate genome-wide profiles of chromatin features and to survey global gene expression programs in ES cells, we describe protocols for efficient library construction for next-generation sequencing of ChIP-Seq and RNA-Seq samples. C1 [Kidder, Benjamin L.; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 14 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 3 EP 20 DI 10.1007/978-1-4939-0512-6_1 D2 10.1007/978-1-4939-0512-6 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100002 PM 24743988 ER PT S AU Kidder, BL AF Kidder, Benjamin L. BE Kidder, BL TI Stem Cell Transcriptional Networks Methods and Protocols Preface SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP V EP V D2 10.1007/978-1-4939-0512-6 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100001 ER PT S AU Xu, SLY Grullon, S Ge, K Peng, WQ AF Xu, Shiliyang Grullon, Sean Ge, Kai Peng, Weiqun BE Kidder, BL TI Spatial Clustering for Identification of ChIP-Enriched Regions (SICER) to Map Regions of Histone Methylation Patterns in Embryonic Stem Cells SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ChIP-Seq; Histone modifications; Epigenetic modifications; Epigenome; SICER ID HUMAN GENOME; LYSINE 9; SEQ DATA; PROTEINS; DOMAINS; H3 AB Chromatin states are the key to embryonic stem cell pluripotency and differentiation. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-Seq) is increasingly used to map chromatin states and to functionally annotate the genome. Many ChIP-Seq profiles, especially those of histone methylations, are noisy and diffuse. Here we describe SICER (Zang et al., Bioinformatics 25(15): 1952-1958, 2009), an algorithm specifically designed to identify disperse ChIP-enriched regions with high sensitivity and specificity. This algorithm has found a lot of applications in epigenomic studies. In this Chapter, we will demonstrate in detail how to run SICER to delineate ChIP-enriched regions and assess their statistical significance, and to identify regions of differential enrichment when two chromatin states are compared. C1 [Xu, Shiliyang; Grullon, Sean; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Xu, Shiliyang; Grullon, Sean; Ge, Kai] NIDDK, Lab Endocrinol & Receptor Biol, Adipocyte Biol & Gene Regulat Sect, NIH, Bethesda, MD USA. [Peng, Weiqun] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA. RP Xu, SLY (reprint author), George Washington Univ, Dept Phys, Washington, DC 20052 USA. OI Ge, Kai/0000-0002-7442-5138 FU Intramural NIH HHS [ZIA DK047055-07, ZIA DK075003-10, ZIA DK075017-05, Z99 DK999999] NR 16 TC 15 Z9 15 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 97 EP 111 DI 10.1007/978-1-4939-0512-6_5 D2 10.1007/978-1-4939-0512-6 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100006 PM 24743992 ER PT S AU Zheng, XF Hu, G AF Zheng, Xiaofeng Hu, Guang BE Kidder, BL TI Use of Genome-Wide RNAi Screens to Identify Regulators of Embryonic Stem Cell Pluripotency and Self-Renewal SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Embryonic stem cell; Self-renewal; Pluripotency; RNAi; Genome-wide; Genetic screen; Reporter assay ID DIFFERENTIATION; MOUSE AB Embryonic stem cells (ESCs) are characterized by two defining features: pluripotency and self-renewal. They hold tremendous promise for both basic research and regenerative medicine. To fully realize their potentials, it is important to understand the molecular mechanisms regulating ESC pluripotency and self-renewal. The development of RNA interference (RNAi) technology has revolutionized functional genetic studies in mammalian cells. In recent years, genome-wide RNAi screens have been adopted to systematically study ESC biology, and have uncovered many previously unknown regulators, including transcription factors, chromatin remodelers, and posttranscriptional modulators. Here, we describe a method for the identification of regulators of ESC pluripotency and self-renewal using RNAi screens, as well as assays for further validation and characterization of the identified candidates. With modifications, this method can also be adapted to study the fate specification events during ESC differentiation. C1 [Zheng, Xiaofeng; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Zheng, XF (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU Intramural NIH HHS [ZIA ES102745-04] NR 12 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 163 EP 173 DI 10.1007/978-1-4939-0512-6_10 D2 10.1007/978-1-4939-0512-6 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100011 PM 24743997 ER PT S AU Hu, GQ Zhao, KJ AF Hu, Gangqing Zhao, Keji BE Kidder, BL TI Correlating Histone Modification Patterns with Gene Expression Data During Hematopoiesis SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Hematopoiesis; Epigenetics; Histone modification; RNA-Seq; ChIP-Seq ID HUMAN GENOME; RNA-SEQ; CELLS; FATE; METHYLATIONS AB Hematopoietic stem cells (HSC) in mammals are an ideal system to study differentiation. While transcription factors (TFs) control the differentiation of HSCs to distinctive terminal blood cells, accumulating evidence suggests that chromatin structure and modifications constitute another critical layer of gene regulation. Recent genome-wide studies based on next-generation sequencing reveal that histone modifications are linked to gene expression and contribute to hematopoiesis. Here, we briefly review the bioinformatics aspects for ChIP-Seq and RNA-Seq data analysis with applications to the epigenetic studies of hematopoiesis and provide a practical guide to several basic data analysis methods. C1 [Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Hu, GQ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RI HU, GANGQING/K-5849-2012 FU Intramural NIH HHS [ZIA HL006031-01] NR 18 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 175 EP 187 DI 10.1007/978-1-4939-0512-6_11 D2 10.1007/978-1-4939-0512-6 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100012 PM 24743998 ER PT S AU Kidder, BL AF Kidder, Benjamin L. BE Kidder, BL TI In Vitro Maturation and In Vitro Fertilization of Mouse Oocytes and Preimplantation Embryo Culture SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE In vitro maturation; In vitro fertilization; IVM; IVF; Oocytes; Ovarian follicle; Cumulus oocyte complex; COC; Blastocyst; Embryo culture; Mouse ID PRIMORDIAL FOLLICLES; PREANTRAL FOLLICLES AB Epigenetic regulation of gene expression in the germline is important for reproductive success of mammals. Misregulation of genes whose expression is correlated with reproductive success may result in subfertility or infertility. To study epigenetic events that occur during oocyte maturation and preimplantation embryo development, it is important to generate large numbers of ovarian follicles and embryos. Oocyte maturation can be modeled using in vitro maturation (IVM), which is a system of maturing ovarian follicles in a culture dish. In addition, fertilization and early embryogenesis can be modeled using in vitro fertilization (IVF), which involves the fertilization of mature oocytes with capacitated sperm in a culture dish. Here, we describe protocols for in vitro maturation (IVM) and in vitro fertilization (IVF) of mouse oocytes and preimplantation embryo culture. These protocols are suitable for the study of oocyte and embryo biology and the production of embryonic mice. C1 NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 191 EP 199 DI 10.1007/978-1-4939-0512-6_12 D2 10.1007/978-1-4939-0512-6 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100013 PM 24743999 ER PT S AU Kidder, BL AF Kidder, Benjamin L. BE Kidder, BL TI Derivation and Manipulation of Trophoblast Stem Cells from Mouse Blastocysts SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Trophoblast stem cells; Trophectoderm; FGF4; Derivation; Blastocyst; Differentiation; RNA interference; shRNA; Lentivirus ID TRANSCRIPTIONAL NETWORKS; PLURIPOTENCY; EMBRYOS; DIFFERENTIATION; SPECIFICATION; TROPHECTODERM; MAINTENANCE; NANOG; FATE AB The trophoblast is the first lineage to undergo differentiation during mammalian development. In the preimplantation blastocyst embryo, two cell types are present including the inner cell mass (ICM) and the trophectoderm (TE). ICM cells exhibit pluripotent potential, or the capacity to give rise to all cells represented in the adult organism, while TE cells are multipotent and are therefore only capable of differentiating into trophoblast lineages represented in the placenta. The TE is essential for implantation of the embryo into the uterine tissue, formation of trophoblast lineages represented in the placenta, and exchange of nutrients and waste between the embryo and the mother. Trophoblast stem (TS) cells, which can be derived from the TE of preimplantation embryos in the presence of external signals such as FGF4, can self-renew indefinitely, and because they are capable of differentiating into epithelial lineages of the trophoblast, TS cells are a useful in vitro model to study the biology of the trophoblast including epigenetic regulation of gene expression. In this chapter we describe protocols for derivation of TS cells from mouse blastocysts, culture conditions that promote self-renewal and differentiation, and methods to transduce TS cells with lentiviral particles encoding shRNAs. These protocols are sufficient for efficient derivation of TS cells and robust RNAi knockdown of target genes in TS cells. C1 NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 201 EP 212 DI 10.1007/978-1-4939-0512-6_13 D2 10.1007/978-1-4939-0512-6 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100014 PM 24744000 ER PT S AU Kidder, BL AF Kidder, Benjamin L. BE Kidder, BL TI Generation of Induced Pluripotent Stem Cells Using Chemical Inhibition and Three Transcription Factors SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Embryonic stem cells; Induced pluripotent stem cells; Reprogramming; Oct4; Sox2; c-Myc; Klf4; Inhibitors; Small molecules; Transformation ID SELF-RENEWAL; FIBROBLASTS; ABSENCE; MOUSE; STATE; MYC AB Generation of induced pluripotent stem (iPS) cells from differentiated cells has traditionally been performed by overexpressing four transcription factors: Oct4, Sox2, Klf4, and c-Myc. However, inclusion of c-Myc in the reprogramming cocktail can lead to expansion of transformed cells that are not fully reprogrammed, and studies have demonstrated that c-Myc reactivation increases tumorigenicity in chimeras and progeny mice. Moreover, chemical inhibition of Wnt signaling has been shown to enhance reprogramming efficiency. Here, we describe a modified protocol for generating iPS cells from murine fibroblasts using chemical inhibition and overexpression of three transcription factors. Using this protocol, we observed robust conversion to iPS cells while maintaining minimal contamination of partially reprogrammed transformed colonies. C1 NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 227 EP 236 DI 10.1007/978-1-4939-0512-6_15 D2 10.1007/978-1-4939-0512-6 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100016 PM 24744002 ER PT J AU Wagner, FF Flegel, WA AF Wagner, Franz F. Flegel, Willy A. TI The Rhesus Site SO TRANSFUSION MEDICINE AND HEMOTHERAPY LA English DT Review DE Rh-Hr blood group system; Antigen D; Rh blood group; Databases as topic; Immunization AB The Rhesus Site is a resource for information of the 'Rhesus' blood group. It is intended for specialists and non-specialists. The website details research in the field relevant for transfusion medicine, immunohematology, and molecular research. Link areas guide to important publications and to methodological resources for Rhesus. Many data originally presented at The Rhesus Site have been formally published later. The 'RhesusBase' section represents the largest database for RHD alleles; the 'RhesusSurveillance' section details the results of the largest prospective observational study on anti-D immunization events in D-positive patients. Visitors to the website are encouraged to explore the intricacies of the most complex blood group gene locus. C1 Univ Ulm, D-89069 Ulm, Germany. Red Cross Blood Serv NSTOB, Springe, Germany. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Wagner, FF (reprint author), Inst Springe, Red Cross Blood Serv NSTOB, Eldagsener Str 38, D-31832 Springe, Germany. EM fwagner@bsd-nstob.de NR 0 TC 3 Z9 3 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-3796 EI 1660-3818 J9 TRANSFUS MED HEMOTH JI Transfus. Med. Hemother. PY 2014 VL 41 IS 5 BP 357 EP 363 DI 10.1159/000366176 PG 7 WC Hematology; Immunology SC Hematology; Immunology GA AQ6AS UT WOS:000342890300007 PM 25538538 ER PT B AU Auerbach, SS Paules, RS AF Auerbach, Scott S. Paules, Richard S. BE Kleinjans, J TI Application of In Vivo Genomics to the Prediction of Chemical-Induced (hepato) Carcinogenesis SO TOXICOGENOMICS-BASED CELLULAR MODELS: ALTERNATIVES TO ANIMAL TESTING FOR SAFETY ASSESSMENT LA English DT Article; Book Chapter ID GENE-EXPRESSION PROFILES; INDUCED HEMOLYTIC-ANEMIA; RODENT CANCER BIOASSAYS; RENAL TUBULAR TOXICITY; RAT-LIVER; SHORT-TERM; PEROXISOME PROLIFERATORS; NONGENOTOXIC MECHANISMS; INDUCED CARDIOTOXICITY; GENOTOXIC MECHANISMS C1 [Auerbach, Scott S.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Paules, Richard S.] NIEHS, Toxicol & Pharmacol Lab, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Auerbach, SS (reprint author), NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 134 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397871-4; 978-0-12-397862-2 PY 2014 BP 15 EP 33 PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB2YM UT WOS:000342568200002 ER PT B AU Fostel, J van Someren, E Pronk, T Pennings, J Schmeits, P Shao, J Kroese, D Stierum, R AF Fostel, Jennifer van Someren, Eugene Pronk, Tessa Pennings, Jeroen Schmeits, Peter Shao, Jia Kroese, Dinant Stierum, Rob BE Kleinjans, J TI Toxicogenomics and Systems Toxicology Databases and Resources: Chemical Effects in Biological Systems (CEBS) and Data Integration by Applying Models on Design and Safety (DIAMONDS) SO TOXICOGENOMICS-BASED CELLULAR MODELS: ALTERNATIVES TO ANIMAL TESTING FOR SAFETY ASSESSMENT LA English DT Article; Book Chapter ID LINE GENE-EXPRESSION; EXCHANGE C1 [Fostel, Jennifer] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [van Someren, Eugene; Stierum, Rob] Netherlands Org Appl Sci Res Microbiol & Syst Bio, Zeist, Netherlands. [Pronk, Tessa; Pennings, Jeroen] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands. [Schmeits, Peter; Shao, Jia] Univ Wageningen & Res Ctr, BU Toxicol & Bioassays, RIKILT Inst Food Safety, Wageningen, Netherlands. [Kroese, Dinant] Netherlands Org Appl Sci Res, Risk Anal Prod Dev, Zeist, Netherlands. RP Fostel, J (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. OI Pronk, Tessa/0000-0002-8699-0257 NR 9 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397871-4; 978-0-12-397862-2 PY 2014 BP 275 EP 290 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB2YM UT WOS:000342568200015 ER PT J AU Resnik, DB AF Resnik, David B. TI Making Sense of the Undue Burden Interpretation of Minimal Risk SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID PEDIATRIC RESEARCH; STANDARD; BENEFIT C1 [Resnik, David B.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2014 VL 14 IS 9 BP 1 EP 2 DI 10.1080/15265161.2014.935880 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AP7YG UT WOS:000342293900001 PM 25127263 ER PT J AU Wendler, D AF Wendler, David TI Justice and Nontherapeutic Pediatric Research SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID MINIMAL RISK C1 [Wendler, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural NIH HHS NR 5 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2014 VL 14 IS 9 BP 13 EP 15 DI 10.1080/15265161.2014.936250 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AP7YG UT WOS:000342293900003 PM 25127265 ER PT J AU Wasserman, D Wertheimer, A AF Wasserman, David Wertheimer, Alan TI In Defense of Bunkering SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Wasserman, David] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Wertheimer, Alan] Natl Inst Hlth, Bethesda, MD USA. RP Wasserman, D (reprint author), Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, 1695 Eastchester Rd,Suite 301, Bronx, NY 10461 USA. EM dtwasserman@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2014 VL 14 IS 9 BP 42 EP 43 DI 10.1080/15265161.2014.935885 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AP7YG UT WOS:000342293900015 PM 25127277 ER PT J AU Nash, TE AF Nash, Theodore E. TI Parasitic Diseases that Cause Seizures SO EPILEPSY CURRENTS LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; CHILDHOOD CEREBRAL MALARIA; VISCERAL LARVA MIGRANS; HUMAN AFRICAN TRYPANOSOMIASIS; FALCIPARUM-MALARIA; NEUROLOGICAL MANIFESTATIONS; NEUROPARASITIC INFECTIONS; PLASMODIUM-FALCIPARUM; CLINICAL-FEATURES; KENYAN CHILDREN AB The propensity of parasites to invade the brain, cause disease, and give rise to seizures and epilepsy varies greatly. This reflects the wide diversity of parasites that differ in fundamental ways. This manuscript reviews parasites that invade the brain or its vasculature and give rise to seizures. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm 126, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov NR 60 TC 2 Z9 3 U1 0 U2 0 PU AMER EPILEPSY SOCIETY PI WEST HARTFORD PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA SN 1535-7597 EI 1535-7511 J9 EPILEPSY CURR JI Epilepsy Curr. PD JAN-FEB PY 2014 VL 14 SU 2 BP 29 EP 34 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AQ0KI UT WOS:000342471800006 PM 24955073 ER PT J AU Theodore, WH AF Theodore, William H. TI Epilepsy and Viral Infections SO EPILEPSY CURRENTS LA English DT Review ID TEMPORAL-LOBE EPILEPSY; HERPES-SIMPLEX ENCEPHALITIS; EASTERN EQUINE ENCEPHALITIS; TICK-BORNE ENCEPHALITIS; NEW-ONSET SEIZURES; CLINICAL-FEATURES; VIRUS-INFECTION; NEUROLOGICAL MANIFESTATIONS; STATUS EPILEPTICUS; DENGUE INFECTION C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NIH, Clin Epilepsy Sect, Bldg 10 Room 7C-103, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 49 TC 2 Z9 2 U1 1 U2 4 PU AMER EPILEPSY SOCIETY PI WEST HARTFORD PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA SN 1535-7597 EI 1535-7511 J9 EPILEPSY CURR JI Epilepsy Curr. PD JAN-FEB PY 2014 VL 14 SU 2 BP 35 EP 42 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AQ0KI UT WOS:000342471800007 PM 24955074 ER PT S AU Mumford, SL Schliep, KC Prasad, A Schisterman, EF AF Mumford, S. L. Schliep, K. C. Prasad, A. Schisterman, E. F. BE HollinsMartin, C VanDenAkker, O Martin, C Preedy, VR TI The menstrual cycle and lipid levels SO HANDBOOK OF DIET AND NUTRITION IN THE MENSTRUAL CYCLE, PERICONCEPTION AND FERTILITY SE Human Health Handbooks LA English DT Article; Book Chapter DE cholesterol; lipoproteins; dietary fiber; estradiol; menstrual cycle ID CARDIOVASCULAR-DISEASE RISK; AMERICAN-HEART-ASSOCIATION; ESTROGEN PLUS PROGESTIN; DIETARY FIBER; POSTMENOPAUSAL WOMEN; PLASMA-LIPIDS; CHOLESTEROL; LIPOPROTEINS; PREMENOPAUSAL; RESPONSES AB Understanding the complex interplay between lipoprotein cholesterol, endogenous hormones, and dietary fiber intake is essential for clinical management of women, as well as for the design and interpretation of studies in reproductive-aged women. Herein, we review the evidence regarding, first, intra-individual variation in lipoprotein cholesterol levels - total, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) - across the menstrual cycle; second, the association between fiber intake and reproductive hormones; and third, the effect of fiber intake on lipoprotein cholesterol mediated by estrogen. Among women of reproductive age, the weight of evidence indicates significant fluctuations in lipoprotein cholesterol levels across the menstrual cycle, with estrogen levels positively associated with HDL-C, and inversely associated with total and LDL-C. Fiber consumption at or above the recommended intakes was significantly associated with lower reproductive hormone concentrations and a higher probability of anovulatory cycles. Moreover, the association between fiber and lipoprotein cholesterol levels was mediated by estrogen, suggesting that high-fiber diets may have reduced effects in premenopausal women. Both women and physicians should take menstrual cycle phase into account when interpreting a woman's cholesterol measurement. Cyclic variations in lipoprotein cholesterol levels have important implications for the design and interpretation of studies among reproductive-age women. C1 [Mumford, S. L.; Schliep, K. C.; Prasad, A.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Rockville, MD 20852 USA. RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA. EM mumfords@mail.nih.gov NR 30 TC 0 Z9 0 U1 0 U2 0 PU WAGENINGEN ACAD PUBL PI WAGENINGEN PA POSTBUS 220, 6700 AE WAGENINGEN, NETHERLANDS SN 2212-375X BN 978-90-8686-767-7; 978-90-8686-212-2 J9 HUM HEALT HANDB PY 2014 IS 7 BP 239 EP 253 DI 10.3920/978-90-8686-767-7_15 D2 10.3920/978-90-8686-767-7 PG 15 WC Nutrition & Dietetics; Reproductive Biology SC Nutrition & Dietetics; Reproductive Biology GA BB2QA UT WOS:000342056700016 ER PT J AU Namima, T Yasuda, M Banno, T Okazawa, G Komatsu, H AF Namima, Tomoyuki Yasuda, Masaharu Banno, Taku Okazawa, Gouki Komatsu, Hidehiko TI Effects of luminance contrast on the color selective responses in macaque V4 and inferior temporal cortex SO I-PERCEPTION LA English DT Meeting Abstract C1 [Namima, Tomoyuki; Okazawa, Gouki; Komatsu, Hidehiko] Natl Inst Physiol Sci, Matsuo, Iwate, Japan. [Namima, Tomoyuki; Komatsu, Hidehiko] Grad Univ Adv Studies SOKENDAI, Kanagawa, Japan. [Yasuda, Masaharu] NEI, NIH, Bethesda, MD USA. [Banno, Taku] Natl Inst Neurosci, Tokyo, Japan. EM namima@nips.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 2041-6695 J9 I-PERCEPTION JI I-Perception PY 2014 VL 5 IS 4 MA O1B-3 BP 215 EP 215 PG 1 WC Psychology, Experimental SC Psychology GA AP9BQ UT WOS:000342373600012 ER PT J AU Park, DU Colt, JS Baris, D Schwenn, M Karagas, MR Armenti, KR Johnson, A Silverman, DT Stewart, PA AF Park, Dong-Uk Colt, Joanne S. Baris, Dalsu Schwenn, Molly Karagas, Margaret R. Armenti, Karla R. Johnson, Alison Silverman, Debra T. Stewart, Patricia A. TI Estimation of the Probability of Exposure to Machining Fluids in a Population-Based Case-Control Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article ID METALWORKING FLUIDS AB We describe an approach for estimating the probability that study subjects were exposed to metalworking fluids (MWFs) in a population-based case-control study of bladder cancer. Study subject reports on the frequency of machining and use of specific MWFs(straight, soluble, and synthetic/semi-synthetic) were used to estimate exposure probability when available. Those reports also were used to develop estimates for job groups, which were then applied to jobs without MWF reports. Estimates using both cases and controls and controls only were developed. The prevalence of machining varied substantially across job groups (0.1 >0.9%), with the greatest percentage of jobs that machined being reported by machinists and tool and die workers. Reports of straight and soluble MWF use were fairly consistent across job groups (generally 50-70%). Synthetic MWF use was lower (13-45%). There was little difference in reports by cases and controls vs. controls only. Approximately, 1% of the entire study population was assessed as definitely exposed to straight or soluble fluids in contrast to 0.2% definitely exposed to synthetic/semi-synthetics. A comparison between the reported use of the MWFs and U.S. production levels found high correlations (r generally >0.7). Overall, the method described here is likely to have provided a systematic and reliable ranking that better reflects the variability of exposure to three types of MWFs than approaches applied in the past. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a list of keywords in the occupational histories that were used to link study subjects to the metalworking fluids (MWFs) modules; recommendations from the literature on selection of MWFs based on type of machining operation, the metal being machined and decade; popular additives to MWFs; the number and proportion of controls who reported various MWF responses by job group; the number and proportion of controls assigned to the MWF types by job group and exposure category; and the distribution of cases and controls assigned various levels of probability by MWF type.] C1 [Park, Dong-Uk; Colt, Joanne S.; Baris, Dalsu; Silverman, Debra T.; Stewart, Patricia A.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Park, Dong-Uk] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea. [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Karagas, Margaret R.] Dartmouth Coll, Geisel Sch Med Dartmouth, Hanover, NH USA. [Armenti, Karla R.] New Hampshire Dept Hlth & Human Serv, Div Publ Hlth Serv, Bur Publ Hlth Stat & Informat, Occupat Hlth Surveillance Program, Concord, NH 03301 USA. [Johnson, Alison] Vermont Dept Hlth, Burlington, VT 05402 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. RP Colt, JS (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 9609 Med Ctr Dr,Room 6E608,MSC 9771, Bethesda, MD 20892 USA. EM coltj@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland FX We thank Lonn Tremblay at IMS Inc. for data programming support. This project was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. NR 26 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1545-9624 EI 1545-9632 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2014 VL 11 IS 11 BP 757 EP 770 DI 10.1080/15459624.2014.918984 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AP7UW UT WOS:000342283700012 PM 25256317 ER PT S AU Hussain, S Garantziotis, S Rodrigues-Lima, F Dupret, JM Baeza-Squiban, A Boland, S AF Hussain, Salik Garantziotis, Stavros Rodrigues-Lima, Fernando Dupret, Jean-Marie Baeza-Squiban, Armelle Boland, Sonja BE Capco, DG Chen, Y TI Intracellular Signal Modulation by Nanomaterials SO NANOMATERIAL: IMPACTS ON CELL BIOLOGY AND MEDICINE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Signaling; Nanotoxicology; Nanomedicine; Oxidative stress; Protein interaction; Cell death; Physico-chemical characteristics ID TITANIUM-DIOXIDE NANOPARTICLES; LUNG EPITHELIAL-CELLS; CERIUM OXIDE NANOPARTICLES; HUMAN DERMAL FIBROBLASTS; WALL CARBON NANOTUBES; AMORPHOUS SILICA NANOPARTICLES; CARBIDE-COBALT NANOPARTICLES; ENDOPLASMIC-RETICULUM STRESS; SIZE-DEPENDENT CYTOTOXICITY; NF-KAPPA-B AB A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways. Induction of the inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed. Furthermore, the uptake mechanisms can be of crucial importance for the cytotoxicity of nanomaterials and membrane-dependent signaling pathways have also been shown to be responsible for cellular effects of nanomaterials. Epigenetic regulation by nanomaterials, effects of nanoparticle-protein interactions on cell signaling pathways, and the induction of various cell death modalities by nanomaterials are described. We describe the common trigger mechanisms shared by various nanomaterials to induce cell death pathways and describe the interplay of different modalities in orchestrating the final outcome after nanomaterial exposures. A better understanding of signal modulations induced by nanomaterials is not only essential for the synthesis and design of safer nanomaterials but will also help to discover potential nanomedical applications of these materials. Several biomedical applications based on the different signaling pathways induced by nanomaterials are already proposed and will certainly gain a great deal of attraction in the near future. C1 [Hussain, Salik; Garantziotis, Stavros] NIEHS, Clin Res Program, NIH, Res Triangle Pk, NC 27709 USA. [Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Baeza-Squiban, Armelle; Boland, Sonja] Univ Paris Diderot, Unit Funct & Adapt Biol BFA, Lab Mol & Cellular Responses Xenobiot RMCX, CNRS EAC 4413,Sorbonne Paris Cite, Paris, France. RP Hussain, S (reprint author), NIEHS, Clin Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM salik.hussain@nih.gov RI Geracitano, Laura/E-6926-2013; Hussain, Salik/O-1687-2016; Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS [Z99 ES999999, ZIA ES102605-07] NR 175 TC 8 Z9 10 U1 2 U2 33 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-94-017-8739-0; 978-94-017-8738-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 811 BP 111 EP 134 DI 10.1007/978-94-017-8739-0_7 D2 10.1007/978-94-017-8739-0 PG 24 WC Nanoscience & Nanotechnology SC Science & Technology - Other Topics GA BB2XG UT WOS:000342453200008 PM 24683030 ER PT J AU Ilinskaya, AN Man, S Patri, AK Clogston, JD Crist, RM Cachau, RE McNeil, SE Dobrovolskaia, MA AF Ilinskaya, Anna N. Man, Sonny Patri, Anil K. Clogston, Jeffrey D. Crist, Rachael M. Cachau, Raul E. McNeil, Scott E. Dobrovolskaia, Marina A. TI Inhibition of phosphoinositol 3 kinase contributes to nanoparticle-mediated exaggeration of endotoxin-induced leukocyte procoagulant activity SO NANOMEDICINE LA English DT Article DE coagulopathy; dendrimer; disseminated intravascular coagulation; leukocyte; nanoparticle; procoagulant activity; thrombosis ID DISSEMINATED INTRAVASCULAR COAGULATION; SUPPORTED LIPID-BILAYERS; TISSUE FACTOR EXPRESSION; IN-VITRO; POLY(AMIDOAMINE) DENDRIMERS; NANOMATERIAL TOXICITY; POLYCATIONIC POLYMERS; HOLE FORMATION; CELL-LINE; ACTIVATION AB Disseminated intravascular coagulation is an increasing concern for certain types of engineered nanomaterials. Recent studies have shed some light on the nanoparticle physicochemical properties contributing to this toxicity; however, the mechanisms are poorly understood. Leukocyte procoagulant activity (PCA) is a key factor contributing to the initiation of this toxicity. We have previously reported on the exaggeration of endotoxin-induced PCA by cationic dendrimers. Herein, we report an effort to discern the mechanism. Materials & methods: Poly(amidoamine) dendrimers with various sizes and surface functionalities were studied in vitro by the recalcification test, flow cytometry and other relevant assays. Results & conclusion: Cationic dendrimers exaggerated endotoxin-induced PCA, but their anionic or neutral counterparts did not; the cationic charge prompts this phenomenon, but different cationic surface chemistries do not influence it. Cationic dendrimers and endotoxin differentially affect the PCA complex. The inhibition of phosphoinositol 3 kinase by dendrimers contributes to the exaggeration of the endotoxin-induced PCA. C1 [Ilinskaya, Anna N.; Man, Sonny; Patri, Anil K.; Clogston, Jeffrey D.; Crist, Rachael M.; McNeil, Scott E.; Dobrovolskaia, Marina A.] NCI Frederick, Adv Technol Program, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Cachau, Raul E.] NCI Frederick, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA. RP Dobrovolskaia, MA (reprint author), NCI Frederick, Adv Technol Program, Nanotechnol Characterizat Lab, SAIC Frederick Inc, 1050 Boyles St,Bldg 469, Frederick, MD 21702 USA. EM marina@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012; Crist, Rachael/K-7603-2012 FU National Cancer Institute, NIH [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 60 TC 4 Z9 4 U1 0 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2014 VL 9 IS 9 BP 1311 EP 1326 DI 10.2217/NNM.13.137 PG 16 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AP4TM UT WOS:000342071700009 PM 24279459 ER PT J AU Chan, CC AF Chan, Chi-Chao TI Aging, Degeneration, Inflammation, Apoptosis: Mechanisms of AMD SO OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 EI 1423-0267 J9 OPHTHALMOLOGICA JI Ophthalmologica PY 2014 VL 232 SU 1 BP 1 EP 1 PG 1 WC Ophthalmology SC Ophthalmology GA AP8WB UT WOS:000342358900002 ER PT J AU Chauchard, E Goncharov, O Krupitsky, E Gorelick, DA AF Chauchard, Emeline Goncharov, Oleg Krupitsky, Evgeny Gorelick, David A. TI Cannabis Withdrawal in Patients With and Without Opioid Dependence SO SUBSTANCE ABUSE LA English DT Article DE Cannabis; opioids; withdrawal ID MARIJUANA USE; ALCOHOL; USERS; POPULATION; SYMPTOMS; ABUSE; ADOLESCENT; TOBACCO AB Background: Cannabis use is common among opioid-dependent individuals, but little is known about cannabis withdrawal in this population. Methods: Thirty inpatients (57% men) completed the Marijuana Quit Questionnaire (MJQQ) after completing acute heroin detoxification treatment in Saint Petersburg, Russia. The MJQQ collected data on motivations for quitting, withdrawal symptoms, and coping strategies used to help maintain abstinence during their most "serious" (self-defined) quit attempt made without formal treatment outside a controlled environment. Results: At the start of their quit attempt, 70% of participants smoked cannabis at least weekly (40% daily), averaging [SD] 2.73 [1.95] joints daily; 60% were heroin dependent. Subjects with heroin dependence were significantly older at the start of their quit attempt (22.9 [3.6] vs. 19.1 [2.9] years), were significantly less likely to report withdrawal irritability/anger/aggression (22% vs. 58%), restlessness (0% vs. 25%), or physical symptoms (6% vs. 33%), or to meet diagnostic criteria for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) cannabis withdrawal syndrome (6% vs. 33%), and had shorter duration of abstinence (29.6 [28.7] vs 73.7 [44.1] months) than those without heroin dependence. Conclusion: Cannabis users with opioid dependence are less likely to experience cannabis withdrawal, suggesting that opiate use may prevent or mask the experience of cannabis withdrawal. Results should be considered preliminary due to small convenience sample and retrospective data. C1 [Chauchard, Emeline] Uni Toulouse Le Mirail, Ctr Etud & Rech Psychopathol CERPP, Toulouse, France. [Chauchard, Emeline; Gorelick, David A.] NIDA, Intramural Res Program, Baltimore, MD USA. [Goncharov, Oleg] North Western State Med Univ, Dept Psychiat, St Petersburg, Russia. [Krupitsky, Evgeny] St Petersburg Bekhterev Psychoneurol Res Inst, Dept Addict, St Petersburg, Russia. RP Gorelick, DA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. EM dgorelick@mprc.umaryland.edu FU Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse; Interministerial Mission for the Fight against Drugs and Drug Addiction (MILDT; French Government); University of Toulouse II, Le Mirail FX This study was supported by the Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse. Dr Chauchard received funding from the Interministerial Mission for the Fight against Drugs and Drug Addiction (MILDT; French Government) and the University of Toulouse II, Le Mirail. The NIH, French Interministerial Mission for the Fight against Drugs and Drug Addiction, and the University of Toulouse II, Le Mirail, played no role in the design or execution of the study, analysis or interpretation of the data, writing of the manuscript, or decision to submit the manuscript for publication. NR 33 TC 1 Z9 2 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 3 BP 230 EP 234 DI 10.1080/08897077.2014.898605 PG 5 WC Substance Abuse SC Substance Abuse GA AP7VA UT WOS:000342284200004 PM 24745656 ER PT J AU Gordon, AJ Galanter, M Khalsa, JH AF Gordon, Adam J. Galanter, Marc Khalsa, Jag H. TI Addressing Addiction Across Borders: An International Perspective on Policies, Scholarship, and Collaboration SO SUBSTANCE ABUSE LA English DT Editorial Material ID SUBSTANCE-ABUSE PREVENTION; SECONDARY-SCHOOL; STUDENTS; KHAT C1 [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Galanter, Marc] NYU, Sch Med, Div Alcoholism & Drug Abuse, New York, NY USA. [Khalsa, Jag H.] NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu NR 18 TC 1 Z9 1 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 3 BP 290 EP 291 DI 10.1080/08897077.2014.929906 PG 2 WC Substance Abuse SC Substance Abuse GA AP7VA UT WOS:000342284200012 PM 24892635 ER PT J AU Jochmanova, I Zhuang, Z Yang, C Pacak, K AF Jochmanova, I Zhuang, Z. Yang, C. Pacak, K. BE Castillo, R Abarquez, RF Aquino, AV Sy, RG Gomez, LA Divinagracia, RA Morales, DD TI A new syndrome of multiple paragangliomas and somatostatinoma associated with polycythemia in females SO 10TH ASIAN-PACIFIC CONGRESS OF HYPERTENSION LA English DT Proceedings Paper CT 10th Asian-Pacific Congress of Hypertension CY FEB 12-15, 2014 CL Cebu, PHILIPPINES ID HIF2A MUTATIONS; SPORADIC PHEOCHROMOCYTOMA; NEUROENDOCRINE TUMORS; GENE-EXPRESSION; HYPOXIA; ERYTHROCYTOSIS; HIF-2-ALPHA; NEUROFIBROMATOSIS; PATHWAY; DISEASE AB Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. When these proteins are dysregulated, they contribute to tumorigenesis and cancer progression. However, mutations in genes encoding the alpha subunits of HIFs (HIF-alpha) have not been previously identified in any cancer and recent findings reveal the important role of HIFs in the development of neuroendocrine tumors causing hypertension, especially pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine-producing tumors derived from chromaffin cells of the extraadrenal paraganglia and adrenal medulla. The occurrence of two or more distinct types of tumors, one of them being PGL, is unusual in a patient, except in hereditary cancer syndromes. Here we present six patients with a new syndrome of PGL associated with polycythemia and somatostatinoma. This syndrome results from novel somatic gain-of-function HIF2A gene mutations, which cause an up-regulation of hypoxia-related genes, including erythropoietin and genes important in cancer biology. C1 [Jochmanova, I] P J Safrik Univ, Fac Med, Dept Internal Med 1, Trieda SNP 1, Kosice 04011, Slovakia. [Jochmanova, I; Pacak, K.] NIH, Natl Inst Child Health & Human Dev, Program Reproduct & Adult Endocrinol, Bethesda, MD 20892 USA. [Zhuang, Z.; Yang, C.] NIH, Natl Inst Neurolog Disorders & Stroke, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Jochmanova, I (reprint author), P J Safrik Univ, Fac Med, Dept Internal Med 1, Trieda SNP 1, Kosice 04011, Slovakia. RI Jochmanova, Ivana/I-9011-2016 OI Jochmanova, Ivana/0000-0003-2346-461X FU Intramural Research Program of the NIH; Eunice Kennedy Shriver NICHD FX We would like to acknowledge the clinical and technical assistance of Joan Nambuba in the production of this manuscript. We also thank patients and their families for their participation and assistance. This research was supported, in part, by the Intramural Research Program of the NIH, Eunice Kennedy Shriver NICHD. NR 56 TC 0 Z9 0 U1 1 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-705-7 PY 2014 BP 1 EP 5 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BB2SF UT WOS:000342215900001 ER PT S AU Wickner, RB Edskes, HK Bateman, DA Kelly, AC Gorkovskiy, A Dayani, Y Zhou, A AF Wickner, Reed B. Edskes, Herman K. Bateman, David A. Kelly, Amy C. Gorkovskiy, Anton Dayani, Yaron Zhou, Albert BE Perrett, S TI Amyloid diseases of yeast: prions are proteins acting as genes SO AMYLOIDS IN HEALTH AND DISEASE SE Essays in Biochemistry LA English DT Review; Book Chapter DE [PIN plus ]; [PSI plus ]; [URE3]; in-register parallel beta-sheet; solid-state NMR; Sup35p; Ure2p ID BETA-SHEET STRUCTURE; 2-MU-M CIRCLE PLASMID; CHAIN RELEASE FACTOR; HET-S PRION; SACCHAROMYCES-CEREVISIAE; ENVIRONMENTAL-STRESS; IN-VITRO; SPECIES BARRIERS; SUP35 PROTEIN; SELFISH DNA AB The unusual genetic properties of the non-chromosomal genetic elements [URE3] and [PSI+] led to them being identified as prions (infectious proteins) of Ure2p and Sup35p respectively. Ure2p and Sup35p, and now several other proteins, can form amyloid, a linear ordered polymer of protein monomers, with a part of each molecule, the prion domain, forming the core of this beta-sheet structure. Amyloid filaments passed to a new cell seed the conversion of the normal form of the protein into the same amyloid form. The cell's phenotype is affected, usually from the deficiency of the normal form of the protein. Solid-state NMR studies indicate that the yeast prion amyloids are in-register parallel beta-sheet structures, in which each residue (e.g. Asn(35)) forms a row along the filament long axis. The favourable interactions possible for aligned identical hydrophilic and hydrophobic residues are believed to be the mechanism for propagation of amyloid conformation. Thus, just as DNA mediates inheritance by templating its own sequence, these proteins act as genes by templating their conformation. Distinct isolates of a given prion have different biological properties, presumably determined by differences between the amyloid structures. Many lines of evidence indicate that the Saccharomyces cerevisiae prions are pathological disease agents, although the example of the [Het-s] prion of Podospora anserina shows that a prion can have beneficial aspects. C1 [Wickner, Reed B.; Edskes, Herman K.; Bateman, David A.; Kelly, Amy C.; Gorkovskiy, Anton; Dayani, Yaron; Zhou, Albert] Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Gorkovskiy, Anton/J-8930-2016 OI Gorkovskiy, Anton/0000-0003-4811-2282 FU Intramural NIH HHS NR 85 TC 5 Z9 5 U1 0 U2 10 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0071-1365 BN 978-1-85578-192-4 J9 ESSAYS BIOCHEM JI Essays Biochem. PY 2014 VL 56 BP 193 EP 205 DI 10.1042/BSE0560193 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB2RR UT WOS:000342182600014 PM 25131596 ER PT J AU Park, SY Guo, XL AF Park, Sang Yoon Guo, Xiaoli TI Adaptor protein complexes and intracellular transport SO BIOSCIENCE REPORTS LA English DT Review DE adaptor protein complex; ARF1; membrane trafficking; polarized sorting; signal recognition ID PROGRESSIVE SPASTIC PARAPLEGIA; SYNAPTIC VESICLE BIOGENESIS; POLARIZED EPITHELIAL-CELLS; HERMANSKY-PUDLAK-SYNDROME; CLATHRIN ADAPTER; AP-3 ADAPTER; INTELLECTUAL DISABILITY; STRUCTURAL BASIS; DEFICIENCY CAUSES; BETA-3A SUBUNIT AB The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky-Pudlak syndrome) and HSP (hereditary spastic paraplegia). C1 [Park, Sang Yoon; Guo, Xiaoli] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Guo, XL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM xliguo@gmail.com RI Guo, Xiaoli/O-3906-2014 FU National Institute of Child Health and Human Development; National Institutes of Health FX This work was supported by the Intramural Programme of National Institute of Child Health and Human Development and National Institutes of Health. NR 85 TC 7 Z9 7 U1 4 U2 19 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0144-8463 EI 1573-4935 J9 BIOSCIENCE REP JI Biosci. Rep. PY 2014 VL 34 BP 381 EP 390 AR e00123 DI 10.1042/BSR20140069 PN 4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AP2YW UT WOS:000341943100007 ER PT S AU Dillman, AA Cookson, MR AF Dillman, Allissa A. Cookson, Mark R. BE Hitzemann, R McWeeney, S TI Transcriptomic Changes in Brain Development SO BRAIN TRANSCRIPTOME SE International Review of Neurobiology LA English DT Review; Book Chapter ID GLUTAMATE-OPERATED CHANNELS; DNA-SEQUENCE DIFFERENCES; HUMAN PREFRONTAL CORTEX; GENE-EXPRESSION; CEREBRAL-CORTEX; MOUSE-BRAIN; NEURONAL DIFFERENTIATION; EMBRYONIC-DEVELOPMENT; MICRORNA EXPRESSION; MICROARRAY ANALYSIS AB The transcriptome changes hugely during development of the brain. Whole genes, alternate exons, and single base pair changes related to RNA editing all show differences between embryonic and mature brain. Collectively, these changes control proteomic diversity as the brain develops. Additionally, there are many changes in noncoding RNAs (miRNA and IncRNA) that interact with mRNA to influence the overall transcriptional landscape. Here, we will discuss what is known about such changes in brain development, particularly focusing on high-throughput approaches and how those can be used to infer mechanisms by which gene expression is controlled in the brain as it matures. C1 [Dillman, Allissa A.; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS [ZIA AG000947-07] NR 83 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-801105-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2014 VL 116 BP 233 EP 250 DI 10.1016/B978-0-12-801105-8.00009-6 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BB2IP UT WOS:000341798600009 PM 25172477 ER PT S AU Zhou, ZF Enoch, MA Goldman, D AF Zhou, Zhifeng Enoch, Mary-Anne Goldman, David BE Hitzemann, R McWeeney, S TI Gene Expression in the Addicted Brain SO BRAIN TRANSCRIPTOME SE International Review of Neurobiology LA English DT Review; Book Chapter ID LONG-TERM POTENTIATION; CORTICOTROPIN-RELEASING-FACTOR; VENTRAL TEGMENTAL AREA; HUMAN COCAINE ABUSERS; IMMEDIATE-EARLY GENE; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; ALCOHOL DEPENDENCE; DNA METHYLATION; RAT HIPPOCAMPUS AB Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by "omic" methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain. C1 [Zhou, Zhifeng; Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, ZF (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM zhouz@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS [Z01 AA000306-02, Z01 AA000280-18] NR 93 TC 5 Z9 7 U1 1 U2 15 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-801105-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2014 VL 116 BP 251 EP 273 DI 10.1016/B978-0-12-801105-8.00010-2 PG 23 WC Neurosciences SC Neurosciences & Neurology GA BB2IP UT WOS:000341798600010 PM 25172478 ER PT J AU Galis, Z AF Galis, Z. TI MOLECULAR DRIVERS OF VASCULAR REMODELING SO CARDIOLOGY LA English DT Meeting Abstract C1 [Galis, Z.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 192 BP 206 EP 206 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400192 ER PT J AU Jang, H Arce, FT Ramachandran, S Kagan, BL Lal, R Nussinov, R AF Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Kagan, Bruce L. Lal, Ratnesh Nussinov, Ruth TI Disordered amyloidogenic peptides may insert into the membrane and assemble into common cyclic structural motifs SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID A-BETA OLIGOMERS; MOLECULAR-DYNAMICS SIMULATIONS; ATOMIC-FORCE MICROSCOPY; FORMS ION CHANNELS; PROTEIN-MISFOLDING DISEASES; ALL-D-ENANTIOMER; ALZHEIMERS-DISEASE; FIBRIL FORMATION; LIPID-BILAYERS; IN-VITRO AB Aggregation of disordered amyloidogenic peptides into oligomers is the causative agent of amyloid-related diseases. In solution, disordered protein states are characterized by heterogeneous ensembles. Among these, beta-rich conformers self-assemble via a conformational selection mechanism to form energetically-favored cross-beta structures, regardless of their precise sequences. These disordered peptides can also penetrate the membrane, and electrophysiological data indicate that they form ion-conducting channels. Based on these and additional data, including imaging and molecular dynamics simulations of a range of amyloid peptides, Alzheimer's amyloid-beta (A beta) peptide, its disease-related variants with point mutations and N-terminal truncated species, other amyloidogenic peptides, as well as a cytolytic peptide and a synthetic gel-forming peptide, we suggest that disordered amyloidogenic peptides can also present a common motif in the membrane. The motif consists of curved, moon-like beta-rich oligomers associated into annular organizations. The motif is favored in the lipid bilayer since it permits hydrophobic side chains to face and interact with the membrane and the charged/polar residues to face the solvated channel pores. Such channels are toxic since their pores allow uncontrolled leakage of ions into/out of the cell, destabilizing cellular ionic homeostasis. Here we detail A beta, whose aggregation is associated with Alzheimer's disease (AD) and for which there are the most abundant data. AD is a protein misfolding disease characterized by a build-up of A beta peptide as senile plaques, neurodegeneration, and memory loss. Excessively produced A beta peptides may directly induce cellular toxicity, even without the involvement of membrane receptors through A beta peptide-plasma membrane interactions. C1 [Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA. [Kagan, Bruce L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Jang, H (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM jangh2@mail.nih.gov; nussinor@helix.nih.gov FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of NIH; Frederick National Lab, Center for Cancer Research FX This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. This research was supported [in part] by the Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 183 TC 19 Z9 19 U1 8 U2 47 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2014 VL 43 IS 19 BP 6750 EP 6764 DI 10.1039/c3cs60459d PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA AP3KK UT WOS:000341974600008 PM 24566672 ER PT J AU Dettmer, AM Suomi, SJ AF Dettmer, Amanda M. Suomi, Stephen J. TI Nonhuman Primate Models of Neuropsychiatric Disorders: Influences of Early Rearing, Genetics, and Epigenetics SO ILAR JOURNAL LA English DT Article DE early life adversity; epigenetics; genetics; neuropsychiatric disorders; nonhuman primate; rhesus macaque ID INFANT RHESUS MACAQUES; EXCESSIVE ALCOHOL-CONSUMPTION; LINKED POLYMORPHIC REGION; CSF MONOAMINE METABOLITE; TOTAL SOCIAL ISOLATION; SEROTONIN TRANSPORTER; ENVIRONMENT INTERACTIONS; PLASMA-CORTISOL; BEHAVIORAL-INHIBITION; MATERNAL SEPARATION AB This report reviews the scientific literature from the past several decades that focuses on nonhuman primates (NHPs) as models of neuropsychiatric disorders, including anxiety, and alcoholism. In particular, we highlight the approaches, advantages, and disadvantages of the rearing, genetic, and epigenetic methodologies behind these studies as a means of evaluating the application of these methods in assessing disorders in NHPs as models of human disease. Finally, we describe the contributions the NHP studies have made to neuropsychiatric research and areas for future research. C1 [Dettmer, Amanda M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, LCE, NIH, Poolesville, MD 20837 USA. [Suomi, Stephen J.] LCE, Bethesda, MD USA. RP Dettmer, AM (reprint author), NIH Anim Ctr, Bldg 112,POB 529, Poolesville, MD 20837 USA. EM dettmera@mail.nih.gov NR 123 TC 5 Z9 5 U1 8 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2014 VL 55 IS 2 BP 361 EP 370 DI 10.1093/ilar/ilu025 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA AP6WK UT WOS:000342218800012 PM 25225312 ER PT J AU Elder, JP Pequegnat, W Ahmed, S Bachman, G Bullock, M Carlo, WA Chandra-Mouli, V Fox, NA Harkness, S Huebner, G Lombardi, J Murry, VM Moran, A Norton, M Mulik, J Parks, W Raikes, HH Smyser, J Sugg, C Sweat, M AF Elder, John P. Pequegnat, Willo Ahmed, Saifuddin Bachman, Gretchen Bullock, Merry Carlo, Waldemar A. Chandra-Mouli, Venkatraman Fox, Nathan A. Harkness, Sara Huebner, Gillian Lombardi, Joan Murry, Velma McBride Moran, Allisyn Norton, Maureen Mulik, Jennifer Parks, Will Raikes, Helen H. Smyser, Joseph Sugg, Caroline Sweat, Michael TI Caregiver Behavior Change for Child Survival and Development in Low- and Middle-Income Countries: An Examination of the Evidence SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ORAL REHYDRATION THERAPY; SCHOOL-BASED INTERVENTION; MATERNAL LIFE-COURSE; SEVERELY MALNOURISHED CHILDREN; REPEAT ADOLESCENT PREGNANCIES; POSITIVE PARENTING PROGRAM; INTIMATE PARTNER VIOLENCE; NURSE HOME VISITATION; KANGAROO MOTHER CARE AB In June of 2012, representatives from more than 80 countries promulgated a Child Survival Call to Action, which called for reducing child mortality to 20 or fewer child deaths per 1,000 live births in every country by 2035. To address the problem of ending preventable child deaths, the U.S. Agency for International Development and the United Nations Children's Fund convened, on June 3-4, 2013, an Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change. Six evidence review teams were established on different topics related to child survival and healthy development to identify the relevant evidence-based interventions and to prepare reports. This article was developed by the evidence review team responsible for identifying the research literature on caregiver change for child survival and development. This article is organized into childhood developmental periods and cross-cutting issues that affect child survival and healthy early development across all these periods. On the basis of this review, the authors present evidence-based recommendations for programs focused on caregivers to increase child survival and promote healthy development. Last, promising directions for future research to change caregivers' behaviors are given. C1 [Elder, John P.; Smyser, Joseph] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA. [Ahmed, Saifuddin] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Bachman, Gretchen] US Agcy Int Dev, Off HIV AIDS, Washington, DC 20523 USA. [Bullock, Merry] Amer Psychol Assoc, Washington, DC 20036 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Chandra-Mouli, Venkatraman] WHO, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Harkness, Sara] Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT USA. [Huebner, Gillian] US Agcy Int Dev, Ctr Children Advers, Washington, DC 20523 USA. [Lombardi, Joan] Bernard van Leer Fdn, Washington, DC USA. [Murry, Velma McBride] Vanderbilt Univ, Peabody Coll, Nashville, TN 37203 USA. [Moran, Allisyn] US Agcy Int Dev, Off Hlth Infect Dis & Nutr, Washington, DC 20523 USA. [Norton, Maureen] US Agcy Int Dev, Off Populat & Reprod Hlth, Washington, DC 20523 USA. [Mulik, Jennifer] PACT, Washington, DC USA. [Parks, Will] United Nations Childrens Fund UNICEF, New York, NY USA. [Raikes, Helen H.] Univ Nebraska, Dept Child Youth & Family Studies, Lincoln, NE USA. [Sugg, Caroline] British Broadcasting Co, London, England. [Sweat, Michael] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Pequegnat, W (reprint author), NIH, 6001 Execut Blvd,Room 6219,MSC 9619, Bethesda, MD 20892 USA. EM wpequegn@mail.nih.gov NR 214 TC 8 Z9 8 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2014 VL 19 SU 1 SI SI BP 25 EP 66 DI 10.1080/10810730.2014.940477 PG 42 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AP4QC UT WOS:000342062000004 PM 25207447 ER PT J AU Velez, LF Sanitato, M Barry, D Alilio, M Apfel, F Coe, G Garcia, A Kaufman, M Klein, J Kutlesic, V Meadowcroft, L Nilsen, W O'Sullivan, G Peterson, S Raiten, D Vorkoper, S AF Velez, Luis F. Sanitato, Mary Barry, Donna Alilio, Martin Apfel, Franklin Coe, Gloria Garcia, Amparo Kaufman, Michelle Klein, Jonathan Kutlesic, Vesna Meadowcroft, Lisa Nilsen, Wendy O'Sullivan, Gael Peterson, Stefan Raiten, Daniel Vorkoper, Susan TI The Role of Health Systems and Policy in Producing Behavior and Social Change to Enhance Child Survival and Development in Low- and Middle-Income Countries: An Examination of the Evidence SO JOURNAL OF HEALTH COMMUNICATION LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; SEVERELY MALNOURISHED CHILDREN; INTENSIVE-CARE-UNIT; LOW-BIRTH-WEIGHT; ENVIRONMENTAL TOBACCO-SMOKE; REDUCES PERINATAL-MORTALITY; CONDITIONAL CASH TRANSFERS; ESSENTIAL NEWBORN CARE; 1ST 5 YEARS; COST-EFFECTIVENESS AB Evidence-based behavior change interventions addressing health systems must be identified and disseminated to improve child health outcomes. Studies of the efficacy of such interventions were identified from systematic searches of the published literature. Two hundred twenty-nine of the initially identified references were judged to be relevant and were further reviewed for the quality and strength of the evidence. Studies were eligible if an intervention addressed policy or health systems interventions, measured relevant behavioral or health outcomes (e.g., nutrition, childhood immunization, malaria prevention and treatment), used at least a moderate quality research design, and were implemented in low- or middle-income countries. Policy or systems interventions able to produce behavior change reviewed included media (e.g., mass media, social media), community mobilization, educational programs (for caregivers, communities, or providers), social marketing, opinion leadership, economic incentives (for both caregiver and provider), health systems strengthening/policy/legislation, and others. Recommendations for policy, practice, and research are given based on fairly strong data across the areas of health service delivery, health workforce, health financing, governance and leadership, and research. C1 [Velez, Luis F.] DePelchin Childrens Ctr, Houston, TX USA. [Sanitato, Mary] US Agcy Int Dev, Bur Global Hlth, Washington, DC 20004 USA. [Barry, Donna] Ctr Amer Progress, Washington, DC USA. [Alilio, Martin; Coe, Gloria] US Agcy Int Dev, Washington, DC 20004 USA. [Apfel, Franklin] World Hlth Commun Associates, Axbridge, Somerset, England. [Garcia, Amparo] US Forest Serv, Washington, DC 20250 USA. [Kaufman, Michelle] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Commun Programs, Baltimore, MD USA. [Klein, Jonathan] Amer Acad Pediat, Elk Grove Village, IL USA. [Kutlesic, Vesna; Raiten, Daniel; Vorkoper, Susan] NIH, Bethesda, MD 20892 USA. [Meadowcroft, Lisa] AMREF, New York, NY USA. [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [O'Sullivan, Gael] Abt Associates Inc, Bethesda, MD USA. [Peterson, Stefan] Karolinska Inst, Stockholm, Sweden. RP Sanitato, M (reprint author), US Agcy Int Dev, Bur Global Hlth, 1300 Penn Ave NW, Washington, DC 20004 USA. EM msanitato@usaid.gov NR 193 TC 5 Z9 5 U1 5 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2014 VL 19 SU 1 SI SI BP 89 EP 121 DI 10.1080/10810730.2014.939313 PG 33 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AP4QC UT WOS:000342062000006 PM 25207449 ER PT J AU Higgs, ES Goldberg, AB Labrique, AB Cook, SH Schmid, C Cole, CF Obregon, RA AF Higgs, Elizabeth S. Goldberg, Allison B. Labrique, Alain B. Cook, Stephanie H. Schmid, Carina Cole, Charlotte F. Obregon, Rafael A. TI Understanding the Role of mHealth and Other Media Interventions for Behavior Change to Enhance Child Survival and Development in Low- and Middle-Income Countries: An Evidence Review SO JOURNAL OF HEALTH COMMUNICATION LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; SHORT MESSAGE SERVICE; AIDS-FREE GENERATION; MOBILE-PHONE; SYSTEMATIC ANALYSIS; IMPROVE ATTENDANCE; HEALTH-WORKERS; CARE; POPULATION; PERSPECTIVES AB Given the high morbidity and mortality among children in low- and middle-income countries as a result of preventable causes, the U.S. government and the United Nations Children's Fund convened an Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change on June 3-4, 2013, in Washington, D.C. This article summarizes evidence for technological advances associated with population-level behavior changes necessary to advance child survival and healthy development in children under 5 years of age in low- and middle-income countries. After a rigorous evidence selection process, the authors assessed science, technology, and innovation papers that used mHealth, social/transmedia, multiplatform media, health literacy, and devices for behavior changes supporting child survival and development. Because of an insufficient number of studies on health literacy and devices that supported causal attribution of interventions to outcomes, the review focused on mHealth, social/transmedia, and multiplatform media. Overall, this review found that some mHealth interventions have sufficient evidence to make topic-specific recommendations for broader implementation, scaling, and next research steps (e.g., adherence to HIV/AIDS antiretroviral therapy, uptake and demand of maternal health service, and compliance with malaria treatment guidelines). While some media evidence demonstrates effectiveness in changing cognitive abilities, knowledge, and attitudes, evidence is minimal on behavioral endpoints linked to child survival. Population level behavior change is necessary to end preventable child deaths. Donors and low- and middle-income countries are encouraged to implement recommendations for informing practice, policy, and research decisions to fully maximize the impact potential of mHealth and multimedia for child survival and development. C1 [Higgs, Elizabeth S.] NIAID, Div Clin Res, Bethesda, MD 20892 USA. [Goldberg, Allison B.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Labrique, Alain B.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Cook, Stephanie H.] Univ Michigan, Sch Publ Hlth, Hlth Behav Hlth Educ Dept, Ann Arbor, MI 48109 USA. [Schmid, Carina] PCI Media Impact, New York, NY USA. [Cole, Charlotte F.] Blue Butterfly Collaborat, Portland, ME USA. [Obregon, Rafael A.] United Nations Childrens Fund, New York, NY USA. RP Higgs, ES (reprint author), NIAID, Div Clin Res, 6700B Rockledge Dr, Bethesda, MD 20892 USA. EM ehiggs@niaid.nih.gov RI Emchi, Karma/Q-1952-2016 NR 60 TC 11 Z9 11 U1 2 U2 23 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2014 VL 19 SU 1 SI SI BP 164 EP 189 DI 10.1080/10810730.2014.929763 PG 26 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AP4QC UT WOS:000342062000009 PM 25207452 ER PT S AU Cui, CH Shurtleff, D Harris, RA AF Cui, Changhai Shurtleff, David Harris, R. Adron BE Cui, C Shurtleff, D Harris, RA TI Neuroimmune Mechanisms of Alcohol and Drug Addiction SO NEUROIMMUNE SIGNALING IN DRUG ACTIONS AND ADDICTIONS SE International Review of Neurobiology LA English DT Review; Book Chapter ID MICROGLIAL ACTIVATION; NUCLEUS-ACCUMBENS; FRONTAL-CORTEX; SYNAPSE INTERACTIONS; BRAIN-DEVELOPMENT; IMMUNE-RESPONSES; CENTRAL AMYGDALA; NEURAL CIRCUITS; TNF-ALPHA; ETHANOL AB Alcohol and other drugs of abuse have significant impacts on the neuroimmune system. Studies have demonstrated that drugs of abuse interact with the neuroimmune system and alter neuroimmune gene expression and signaling, which in turn contribute to various aspects of addiction. As the key component of the CNS immune system, neuroimmune factors mediate neuroinflammation and modulate a wide range of brain function including neuronal activity, endocrine function, and CNS development. These neuromodulatory properties of immune factors, together with their essential role in neuroinflammation, provide a new framework to understand neuroimmune mechanisms mediating brain functional and behavioral changes contributing to addiction. This chapter highlights recent advances in understanding neuroimmune changes associated with exposure to alcohol and other drugs of abuse, including opiates, marijuana, methamphetamine, and cocaine. It provides a brief overview on what we know about neuroimmune signaling and its role in drug action and addiction. C1 [Cui, Changhai] NIAAA, Bethesda, MD 20892 USA. [Shurtleff, David] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Harris, R. Adron] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. RP Cui, CH (reprint author), NIAAA, Bethesda, MD 20892 USA. EM changhai.cui@nih.gov FU NIAAA NIH HHS [U01 AA013520] NR 78 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-801284-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2014 VL 118 BP 1 EP 12 DI 10.1016/B978-0-12-801284-0.00001-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BB2IQ UT WOS:000341798700001 PM 25175859 ER PT B AU Rapoport, SI Taha, A AF Rapoport, Stanley I. Taha, Ameer BE Watson, RR DeMeester, F TI Imaging Brain DHA Metabolism in Vivo, in Animals, and Humans SO OMEGA-3 FATTY ACIDS IN BRAIN AND NEUROLOGICAL HEALTH LA English DT Article; Book Chapter ID DOCOSAHEXAENOIC ACID METABOLISM; ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; N-3 PUFA DEPRIVATION; POSITRON-EMISSION-TOMOGRAPHY; ARACHIDONIC-ACID; PHOSPHOLIPASE A(2); RAT-BRAIN; UNANESTHETIZED RATS; NUTRITIONAL DEPRIVATION C1 [Rapoport, Stanley I.; Taha, Ameer] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 83 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-410547-8; 978-0-12-410527-0 PY 2014 BP 265 EP 275 DI 10.1016/B978-0-12-410527-0.00022-3 PG 11 WC Biochemistry & Molecular Biology; Clinical Neurology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Nutrition & Dietetics GA BB2ES UT WOS:000341710100023 ER PT J AU Muller, L Jackson, SN Woods, AS AF Muller, Ludovic Jackson, Shelley N. Woods, Amina S. TI ETD and sequential ETD localize the residues involved in D2-A2A heteromerization SO RSC ADVANCES LA English DT Article ID IONIZATION MASS-SPECTROMETRY; ASSISTED-LASER-DESORPTION/IONIZATION; ELECTRON-CAPTURE DISSOCIATION; GAS-PHASE STABILITY; NONCOVALENT COMPLEXES; ESI-MS; PHOSPHATE; PEPTIDE; BINDING; DNA AB Certain amino acid residues and posttranslational modifications play an important role in the formation of noncovalent complexes (NCXs) by electrostatic interactions. Electrospray ionization mass spectrometry (ESI-MS) is the most widely used MS technique for the study of NCXs, due to its softer ionization process and compatibility with the solution phase of NCX mixtures. In order to locate the site where interactions are forming in NCXs involving phosphopeptides and adjacent arginines, tandem mass spectrometry studies using collision-induced dissociation (CID) and electron transfer dissociation (ETD) were performed on NCXs at different charge states. CID fragmentation revealed two dissociation pathways: one in which the electrostatic interaction is disrupted and another in which the covalent bond attaching the phosphate group to the amino acid residue is cleaved, while the electrostatic interaction is maintained. ETD and sequential ETD/ETD, and CID/ETD allow the determination of the NCX interaction site. These results confirmed the involvement of the phosphorylated amino acid and at least two adjacent arginines as the binding site. C1 [Muller, Ludovic; Jackson, Shelley N.; Woods, Amina S.] NIDA, Struct Biol Unit, IRP, NIH, Baltimore, MD 21224 USA. [Muller, Ludovic] Univ Pittsburgh, Pittsburgh, PA USA. RP Woods, AS (reprint author), NIDA, Struct Biol Unit, IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov NR 41 TC 3 Z9 3 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 80 BP 42272 EP 42277 DI 10.1039/c4ra04757e PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA AP6PF UT WOS:000342199000008 ER PT J AU Nicol, B Yao, HHC AF Nicol, Barbara Yao, Humphrey H. -C. TI Building an Ovary: Insights into Establishment of Somatic Cell Lineages in the Mouse SO SEXUAL DEVELOPMENT LA English DT Article DE Development; FOXL2; Granulosa cells; Ovary; Sex determination; Theca cells; WNT pathway ID MAMMALIAN SEX DETERMINATION; TRANSCRIPTION FACTOR FOXL2; THECA-INTERSTITIAL CELLS; PRIMORDIAL GERM-CELLS; GRANULOSA-CELLS; BETA-CATENIN; GENE-EXPRESSION; DETERMINATION REVEALS; TESTIS ORGANOGENESIS; LUTEINIZING-HORMONE AB The molecular pathways that drive the differentiation of somatic cell populations in the testis and ovary have been the subjects of intensive research over the past decade. It is now clear that ovarian differentiation is a coordinate event driven by secreted factors including R-spondin1, WNT4, and follistatin and transcriptional regulators such as beta-catenin and FOXL2. These factors direct bipotential somatic cell lineages toward an ovarian fate and simultaneously suppress the emergence of testis-determining processes. This review summarizes the molecular pathways responsible for establishment of the ovary and discusses the current hypotheses on the origin(s) of somatic cell lineages and how these somatic cells acquire the characteristics necessary for their function during ovarian development and maintenance. (C) 2014 S. Karger AG, Basel C1 [Nicol, Barbara; Yao, Humphrey H. -C.] NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Yao, HHC (reprint author), NIEHS, Lab Reprod & Dev Toxicol, 111 TW Alexander Dr,Mail Drop C4-10, Res Triangle Pk, NC 27709 USA. EM humphrey.yao@nih.gov RI Yao, Humphrey Hung-Chang/B-4795-2010; OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469; Nicol, Barbara/0000-0002-3434-0658 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX We thank all the members of the Yao lab for their helpful comments. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 98 TC 8 Z9 8 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 EI 1661-5433 J9 SEX DEV JI Sex. Dev. PY 2014 VL 8 IS 5 BP 243 EP 251 DI 10.1159/000358072 PG 9 WC Developmental Biology SC Developmental Biology GA AP1HT UT WOS:000341819900005 PM 24480990 ER PT J AU Chandran, PL Dimitriadis, EK Lisziewicz, J Speransky, V Horkay, F AF Chandran, Preethi L. Dimitriadis, Emilios K. Lisziewicz, Julianna Speransky, Vlad Horkay, Ferenc TI DNA nanoparticles with core-shell morphology SO SOFT MATTER LA English DT Article ID VIVO GENE DELIVERY; IN-VIVO; PEI/DNA COMPLEXES; STEM-CELLS; POLYETHYLENIMINE; CONDENSATION; INDENTATION; SPECTROSCOPY; PARTICLES; CAPSULES AB Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate nanoparticles of DNA that can be targeted to the antigen-presenting cells of the immune system. We report that the sugar modification alters the DNA organization within the nanoparticles from homogenous to shell-like packing. The depth-dependent packing of DNA within the nanoparticles was probed using AFM nano-indentation. Unmodified PEI-DNA nanoparticles display linear elastic properties and depth-independent mechanics, characteristic of homogenous materials. Mannobiose-modified nanoparticles, however, showed distinct force regimes that were dependent on indentation depth, with 'buckling'-like response that is reproducible and not due to particle failure. By comparison with theoretical studies of spherical shell mechanics, the structure of mannobiosylated particles was deduced to be a thin shell with wall thickness in the order of few nanometers, and a fluid-filled core. The shell-core structure is also consistent with observations of nanoparticle denting in altered solution conditions, with measurements of nanoparticle water content from AFM images, and with images of DNA distribution in Transmission Electron Microscopy. C1 [Chandran, Preethi L.; Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. [Chandran, Preethi L.; Dimitriadis, Emilios K.; Speransky, Vlad] NIBIB, NIH, Bethesda, MD 20892 USA. [Lisziewicz, Julianna] eMMUNITY Inc, Bethesda, MD 20814 USA. RP Chandran, PL (reprint author), Howard Univ, Dept Chem Engn, Washington, DC 20059 USA. EM chandranlp@mail.nih.gov; horkay@helix.nih.gov FU NICHD, NIH FX This research was supported by the Intramural Research Program of the NICHD, NIH. The authors are grateful to Mr Quentinn Roby and Mr Ayele Guggsaa at Howard University for their assistance with the TEM imaging of PEI nanoparticles. NR 45 TC 2 Z9 2 U1 1 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X EI 1744-6848 J9 SOFT MATTER JI Soft Matter PY 2014 VL 10 IS 38 BP 7653 EP 7660 DI 10.1039/c4sm00908h PG 8 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA AP4VS UT WOS:000342077900024 PM 25137385 ER PT J AU Plank, JL Suflita, MT Galindo, CL Labosky, PA AF Plank, Jennifer L. Suflita, Michael T. Galindo, Cristi L. Labosky, Patricia A. TI Transcriptional targets of Foxd3 in murine ES cells SO STEM CELL RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; SKELETAL-MUSCLE; SELF-RENEWAL; MOUSE DEVELOPMENT; GENE-EXPRESSION; PROTEIN FAMILY; DIFFERENTIATION; APOPTOSIS; SOX15; PLURIPOTENCY AB Understanding gene regulatory networks controlling properties of pluripotent stem cells will facilitate development of stem cell-based therapies. The transcription factor Foxd3 is critical for maintenance of self-renewal, survival, and pluripotency in murine embryonic stem cells (ESCs). Using a conditional deletion of Foxd3 followed by gene expression analyses, we demonstrate that genes required for several developmental processes including embryonic organ development, epithelium development, and epithelial differentiation were misregulated in the absence of Foxd3. Additionally, we identified 6 novel targets of Foxd3 (Sox4, Safb, Sox15, Fosb, Pmaip1 and Smarcd3). Finally, we present data suggesting that Foxd3 functions upstream of genes required for skeletal muscle development. Together, this work provides further evidence that Foxd3 is a critical regulator of murine development through the regulation of lineage specific differentiation. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved. C1 [Plank, Jennifer L.; Suflita, Michael T.; Labosky, Patricia A.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37235 USA. [Plank, Jennifer L.; Suflita, Michael T.; Labosky, Patricia A.] Vanderbilt Univ, Ctr Stem Cell Biol, Nashville, TN 37235 USA. [Galindo, Cristi L.] Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Plank, JL (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, 50 South Dr,Bldg 50-3152, Bethesda, MD 20892 USA. EM jennifer.plank@nih.gov FU NIH [R01HD036720, 5P01GM085354, T32HD007043, U01HL100398]; Vanderbilt University Medical Center Academic Support program; AHA [10PRE4500024] FX We thank Adam Bazinet and Drs. Steve Dalton and Ali Brivanlou for their careful reading of this manuscript. P. A. L. was supported by NIH R01HD036720, a pilot grant from NIH 5P01GM085354, and the Vanderbilt University Medical Center Academic Support program. J.L.P. was supported by AHA 10PRE4500024. M. T. S. was supported by NIH T32HD007043. C. L. G. was supported by NIH U01HL100398. NR 48 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD JAN PY 2014 VL 12 IS 1 BP 233 EP 240 DI 10.1016/j.scr.2013.10.008 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AP7VR UT WOS:000342286200019 PM 24270162 ER PT S AU Ren, L Khanna, C AF Ren, Ling Khanna, Chand BE Kleinerman, ES TI Role of Ezrin in Osteosarcoma Metastasis SO CURRENT ADVANCES IN OSTEOSARCOMA SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Ezrin; ERM Proteins; Osteosarcoma; Metastasis; Sarcoma ID SQUAMOUS-CELL CARCINOMA; EZRIN/RADIXIN/MOESIN ERM PROTEINS; SOFT-TISSUE SARCOMAS; T-LYMPHOCYTES; MEDIATED PHOSPHORYLATION; MOESIN PHOSPHORYLATION; CLINICAL-IMPLICATIONS; CYTOPLASMIC DOMAIN; PROGNOSTIC-FACTORS; CANCER METASTASIS AB The cause of death for the vast majority of cancer patients is the development of metastases at sites distant from that of the primary tumor. For most pediatric sarcoma patients such as those with osteosarcoma (OS), despite successful management of the primary tumor through multimodality approaches, the development of metastases, commonly to the lungs, is the cause of death. Significant improvements in long-term outcome for these patients have not been seen in more than 30 years. Furthermore, the long-term outcome for patients who present with metastatic disease is grave [1-5]. New treatment options are needed. Opportunities to improve outcomes for patients who present with metastases and those at-risk for progression and metastasis require an improved understanding of cancer progression and metastasis. With this goal in mind we and others have identified ezrin as a metastasis-associated protein that associated with OS and other cancers. Ezrin is the prototypical ERM (Ezrin/Radixin/Moesin) protein family member. ERMs function as linker proteins connecting the actin cytoskeleton and the plasma membrane. Since our initial identification of ezrin in pediatric sarcoma, an increasing understanding the role of ezrin in metastasis has emerged. Briefly, ezrin appears to allow metastatic cells to overcome a number of stresses experienced during the metastatic cascade, most notably the stress experienced as cells interact with the microenvironment of the secondary site. Cells must rapidly adapt to this environment in order to survive. Evidence now suggests a connection between ezrin expression and a variety of mechanisms linked to this important cellular adaptation including the ability of metastatic cells to initiate the translation of new proteins and to allow the efficient generation of ATP through a variety of sources. This understanding of the role of ezrin in the biology of metastasis is now sufficient to consider ezrin as an important therapeutic target in osteosarcoma patients. This chapter reviews our understanding of ezrin and the related ERM proteins in normal tissues and physiology, summarizes the expression of ezrin in human cancers and associations with clinical parameters of disease progression, reviews reports that detail a biological understanding of ezrin's role in metastatic progression, and concludes with a rationale that may be considered to target ezrin and ezrin biology in osteosarcoma. C1 [Ren, Ling; Khanna, Chand] NCI, Mol Oncol Sect, Metastasis Biol Grp, Pediat Oncol Branch,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Mol Oncol Sect, Metastasis Biol Grp, Pediat Oncol Branch,Ctr Canc Res,NIH, 37 Convent Dr,Rm 2144, Bethesda, MD 20892 USA. EM renl@mail.nih.gov; khannac@mail.nih.gov FU Intramural NIH HHS NR 122 TC 17 Z9 19 U1 2 U2 13 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-04843-7; 978-3-319-04842-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 804 BP 181 EP 201 DI 10.1007/978-3-319-04843-7_10 D2 10.1007/978-3-319-04843-7 PG 21 WC Oncology; Cell Biology SC Oncology; Cell Biology GA BB1YV UT WOS:000341485500011 PM 24924175 ER PT J AU Seitz, H Muller, M AF Seitz, Hanna Mueller, Martin TI Current perspectives on HPV vaccination: a focus on targeting the L2 protein SO FUTURE VIROLOGY LA English DT Review DE cervical cancer; emerging HPV-associated diseases; human papillomavirus; major capsid protein L1-based virus-like particle vaccines; markers for protection; minor capsid protein L2-based cross-protective vaccines; neutralizing antibodies; nonavalent VLP vaccine; second-generation HPV vaccine; vaccine accessibility and production/distribution costs ID VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS TYPE-16; MINOR CAPSID PROTEIN; CERVICAL-CARCINOMA CELLS; RECURRENT RESPIRATORY PAPILLOMATOSIS; HIV-INFECTED CHILDREN; YOUNG-WOMEN; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; BOVINE PAPILLOMAVIRUS AB Thirty years ago, human papillomavirus types 16 and 18 were isolated from cervical carcinomas, and it has been almost 10 years since the introduction of the first prophylactic virus-like particle (VLP) vaccine. The VLP vaccines have already impacted the reduction of pre-malignant lesions and genital warts, and it is expected that vaccination efforts will successfully lower the incidence of cervical cancer before the end of the decade. Here we summarize the historical developments leading to the prophylactic HPV vaccines and discuss current advances of next-generation vaccines that aim to overcome certain limitations of the VLP vaccines, including their intrinsic narrow range of protection, stability and production/distribution costs. C1 [Seitz, Hanna] NCI, NIH, CCR, LCO, Bethesda, MD 20892 USA. [Mueller, Martin] Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. RP Muller, M (reprint author), Deutsch Krebsforschungszentrum, F035,Neuenheimer Feld 242, D-69120 Heidelberg, Germany. EM martin.mueller@dkfz.de NR 146 TC 1 Z9 1 U1 1 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PY 2014 VL 9 IS 7 BP 633 EP 653 DI 10.2217/FVL.14.44 PG 21 WC Virology SC Virology GA AP0RO UT WOS:000341771000009 ER PT J AU Stockman, JK Lucea, MB Bolyard, R Bertand, D Callwood, GB Sharps, PW Campbell, DW Campbell, JC AF Stockman, Jamila K. Lucea, Marguerite B. Bolyard, Richelle Bertand, Desiree Callwood, Gloria B. Sharps, Phyllis W. Campbell, Doris W. Campbell, Jacquelyn C. TI Intimate partner violence among African American and African Caribbean women: prevalence, risk factors, and the influence of cultural attitudes SO GLOBAL HEALTH ACTION LA English DT Article DE intimate partner violence; intimate partner abuse; cultural attitudes; African American; African Caribbean; women ID SAMPLE AB Background: Women of African descent are disproportionately affected by intimate partner abuse; yet, limited data exist on whether the prevalence varies for women of African descent in the United States and those in the US territories. Objective: In this multisite study, we estimated lifetime and 2-year prevalence of physical, sexual, and psychological intimate partner abuse (IPA) among 1,545 women of African descent in the United States and US Virgin Islands (USVI). We also examined how cultural tolerance of physical and/or sexual intimate partner violence (IPV) influences abuse. Design: Between 2009 and 2011, we recruited African American and African Caribbean women aged 18-55 from health clinics in Baltimore, MD, and St. Thomas and St. Croix, USVI, into a comparative case-control study. Screened and enrolled women completed an audio computer-assisted self-interview. Screening-based prevalence of IPA and IPV were stratified by study site and associations between tolerance of IPV and abuse experiences were examined by multivariate logistic regression analysis. Results: Most of the 1,545 screened women were young, of low-income, and in a current intimate relationship. Lifetime prevalence of IPA was 45% in St. Thomas, 38% in St. Croix, and 37% in Baltimore. Lifetime prevalence of IPV was 38% in St. Thomas, 28% in St. Croix, and 30% in Baltimore. Past 2-year prevalence of IPV was 32% in St. Thomas, 22% in St. Croix, and 26% in Baltimore. Risk and protective factors for IPV varied by site. Community and personal acceptance of IPV were independently associated with lifetime IPA in Baltimore and St. Thomas. Conclusions: Variance across sites for risk and protective factors emphasizes cultural considerations in sub-populations of women of African descent when addressing IPA and IPV in given settings. Individual-based interventions should be coupled with community/societal interventions to shape attitudes about use of violence in relationships and to promote healthy relationships. C1 [Stockman, Jamila K.] Univ Calif San Diego, Div Global Publ Hlth, Dept Med, La Jolla, CA 92093 USA. [Lucea, Marguerite B.; Bolyard, Richelle; Sharps, Phyllis W.; Campbell, Jacquelyn C.] Johns Hopkins Univ, Sch Nursing, Dept Community Publ Hlth, Baltimore, MD USA. [Bertand, Desiree; Callwood, Gloria B.; Campbell, Doris W.] Univ Virgin Isl, Caribbean Exploratory NIMHD Res Ctr, Sch Nursing, St Thomas, VI USA. RP Stockman, JK (reprint author), Univ Calif San Diego, Div Global Publ Hlth, Dept Med, 9500 Gilman Dr,MC 0849, La Jolla, CA 92093 USA. EM jstockman@ucsd.edu FU National Institute on Minority Health and Health Disparities [P20MD002286, L60MD003701, L60MD006272]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD077891, T32HD064428]; National Institute on Drug Abuse [K01DA031593]; National Institute of Mental Health [R25MH080664, R25MH080665] FX The authors declare that they have no conflict of interests. This research was supported by a P20 grant (P20MD002286) awarded to the Caribbean Exploratory Research Center, University of the Virgin Islands, from the National Institute on Minority Health and Health Disparities. JKS is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD077891), the National Institute on Drug Abuse (K01DA031593), the National Institute on Minority Health and Health Disparities (L60MD003701), and the National Institute of Mental Health (R25MH080664 and R25MH080665). MBL is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD064428) and the National Institute on Minority Health and Health Disparities (L60MD006272). The contents of this article are solely the responsibility of the authors and do not necessarily represent the ocial views of the National Institutes of Health. NR 27 TC 8 Z9 8 U1 2 U2 10 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1654-9880 J9 GLOBAL HEALTH ACTION JI Glob. Health Action PY 2014 VL 7 AR 24772 DI 10.3402/gha.v7.24772 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AP0PZ UT WOS:000341766000001 PM 25226418 ER PT B AU Bernardi, L Keim, S Klarner, A AF Bernardi, Laura Keim, Sylvia Klaerner, Andreas BE Dominguez, S Hollstein, B TI Social Networks, Social Influence, and Fertility in Germany: Challenges and Benefits of Applying a Parallel Mixed Methods Design SO MIXED METHODS SOCIAL NETWORKS RESEARCH: DESIGN AND APPLICATIONS SE Structural Analysis in the Social Sciences LA English DT Article; Book Chapter ID WESTERN-GERMANY; PARENTAL ATTITUDES; PERSONAL NETWORKS; WEAK TIES; INTENTIONS; BEHAVIOR; SUPPORT; IMPACT; TRANSITIONS; CHILDREN C1 [Bernardi, Laura] Univ Lausanne, CH-1015 Lausanne, Switzerland. [Bernardi, Laura] Max Planck Gesell, Jena, Germany. [Bernardi, Laura] US Natl Inst Hlth, Bethesda, MD USA. [Keim, Sylvia] Univ Rostock, Inst Sociol & Demog, D-18055 Rostock, Germany. [Klaerner, Andreas] Univ Hamburg, Hamburg, Germany. [Klaerner, Andreas] Univ Rostock, D-18055 Rostock, Germany. RP Bernardi, L (reprint author), Univ Lausanne, CH-1015 Lausanne, Switzerland. NR 71 TC 3 Z9 3 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-63105-2; 978-1-107-02792-3 J9 STRUC AN S PY 2014 BP 121 EP 152 D2 10.1017/CBO9781139227193 PG 32 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA BA9QE UT WOS:000339714500006 ER PT B AU Ray, K Hudak, K Citrin, D Stick, M AF Ray, Kausik Hudak, Kathryn Citrin, Deborah Stick, Melissa BE Gupta, RC TI Biomarkers of radiation injury and response SO BIOMARKERS IN TOXICOLOGY LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; IONIZING-RADIATION; DNA-DAMAGE; TRANSCRIPTIONAL RESPONSES; PROTEIN BIOMARKERS; HUMAN-CELLS; IN-VIVO; EXPOSURE; CANCER; THERAPY C1 [Ray, Kausik; Stick, Melissa] NIDOCD, Sci Review Branch, Div Extramural Act, NIH, Bethesda, MD 20892 USA. [Hudak, Kathryn] NIH, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD USA. [Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD USA. RP Ray, K (reprint author), NIDOCD, Sci Review Branch, Div Extramural Act, NIH, Bethesda, MD 20892 USA. NR 78 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-404649-8; 978-0-12-404630-6 PY 2014 BP 673 EP 687 DI 10.1016/B978-0-12-404630-6.00039-7 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB1MX UT WOS:000341214100040 ER PT B AU Reed, CE Fenton, SE AF Reed, Casey E. Fenton, Suzanne E. BE Gupta, RC TI Risk factors as biomarkers of susceptibility in breast cancer SO BIOMARKERS IN TOXICOLOGY LA English DT Article; Book Chapter ID MAMMARY-GLAND DEVELOPMENT; VITAMIN-D DEFICIENCY; EARLY-LIFE; COLLABORATIVE REANALYSIS; ENVIRONMENTAL EXPOSURES; ENDOCRINE DISRUPTORS; KLINEFELTER SYNDROME; PRENATAL EXPOSURE; INDIVIDUAL DATA; MATERNAL RISK C1 [Reed, Casey E.; Fenton, Suzanne E.] NIEHS, Natl Toxicol Program NTP, Labs Branch, Div NTP,NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Reed, CE (reprint author), NIEHS, Natl Toxicol Program NTP, Labs Branch, Div NTP,NIH,Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. NR 88 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-404649-8; 978-0-12-404630-6 PY 2014 BP 743 EP 758 DI 10.1016/B978-0-12-404630-6.00044-0 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB1MX UT WOS:000341214100045 ER PT J AU Turnbull, AE Lau, BM Ruhl, AP Mendez-Tellez, PA Shanholtz, CB Needham, DM AF Turnbull, Alison E. Lau, Bryan M. Ruhl, A. Parker Mendez-Tellez, Pedro A. Shanholtz, Carl B. Needham, Dale M. TI Age and decisions to limit life support for patients with acute lung injury: a prospective cohort study SO CRITICAL CARE LA English DT Article ID INTENSIVE-CARE-UNIT; CUMULATIVE INCIDENCE FUNCTIONS; CAUSE-SPECIFIC HAZARDS; SERIOUSLY ILL; CARDIOPULMONARY-RESUSCITATION; MECHANICAL VENTILATION; COMPETING RISKS; HOSPITALIZED ADULTS; DOSE-RESPONSE; OUTCOMES AB Introduction: The proportion of elderly Americans admitted to the intensive care unit (ICU) in the last month of life is rising. Hence, challenging decisions regarding the appropriate use of life support are increasingly common. The objective of this study was to estimate the association between patient age and the rate of new limitations in the use of life support, independent of daily organ dysfunction status, following acute lung injury (ALI) onset. Methods: This was a prospective cohort study of 490 consecutive patients without any limitations in life support at the onset of ALI. Patients were recruited from 11 ICUs at three teaching hospitals in Baltimore, Maryland, USA, and monitored for the incidence of six pre-defined limitations in life support, with adjustment for baseline comorbidity and functional status, duration of hospitalization before ALI onset, ICU severity of illness, and daily ICU organ dysfunction score. Results: The median patient age was 52 (range: 18 to 96), with 192 (39%) having a new limitation in life support in the ICU. Of patients with a new limitation, 113 (59%) had life support withdrawn and died, 53 (28%) died without resuscitation, and 26 (14%) survived to ICU discharge. Each ten-year increase in patient age was independently associated with a 24% increase in the rate of limitations in life support (Relative Hazard 1.24; 95% CI 1.11 to 1.40) after adjusting for daily ICU organ dysfunction score and all other covariates. Conclusions: Older critically ill patients are more likely to have new limitations in life support independent of their baseline status, ICU-related severity of illness, and daily organ dysfunction status. Future studies are required to determine whether this association is a result of differences in patient preferences by age, or differences in the treatment options discussed with the families of older versus younger patients. C1 [Turnbull, Alison E.; Ruhl, A. Parker; Mendez-Tellez, Pedro A.; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Outcomes After Crit Illness & Surg OACIS Grp, Baltimore, MD 21205 USA. [Turnbull, Alison E.; Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Lau, Bryan M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Ruhl, A. Parker] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Mendez-Tellez, Pedro A.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. [Shanholtz, Carl B.] Univ Maryland, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21287 USA. RP Turnbull, AE (reprint author), Johns Hopkins Univ, Sch Med, Outcomes After Crit Illness & Surg OACIS Grp, 1830 E Monument St 5th Floor, Baltimore, MD 21205 USA. EM turnbull@jhmi.edu OI Shanholtz, Carl/0000-0003-3938-178X FU National Institutes of Health (Acute Lung Injury Specialized Centers of Clinically Oriented Research grant) [P050 HL 73994]; Johns Hopkins University Sommer Scholars Program; National Institute on Aging [T32AG000247] FX This research was supported by the National Institutes of Health (Acute Lung Injury Specialized Centers of Clinically Oriented Research grant number P050 HL 73994). AET is supported by the Johns Hopkins University Sommer Scholars Program and a postdoctoral training grant from the National Institute on Aging, T32AG000247. The authors declare that they have no competing interests. NR 40 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 3 AR R107 DI 10.1186/cc13890 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA AO2OI UT WOS:000341163800021 PM 24886945 ER PT S AU Trudeau, LE Hnasko, TS Wallen-Mackenzie, A Morales, M Rayport, S Sulzer, D AF Trudeau, Louis-Eric Hnasko, Thomas S. Wallen-Mackenzie, Asa Morales, Marisela Rayport, Steven Sulzer, David BE Diana, M DiChiara, G Spano, P TI The multilingual nature of dopamine neurons SO DOPAMINE SE Progress in Brain Research LA English DT Review; Book Chapter DE dopamine; glutamate; GABA; cotransmission; vesicular ID VENTRAL TEGMENTAL AREA; VESICULAR GLUTAMATE TRANSPORTERS; ADULT-RAT NEOSTRIATUM; SUBSTANTIA-NIGRA; NUCLEUS-ACCUMBENS; QUANTAL SIZE; IN-VIVO; SEROTONINERGIC NEURONS; NIGROSTRIATAL NEURONS; TYROSINE-HYDROXYLASE AB The ability of dopamine (DA) neurons to release other transmitters in addition to DA itself has been increasingly recognized, hence the concept of their multilingual nature. A subset of DA neurons, mainly found in the ventral tegmental area, express VGLUT2, allowing them to package and release glutamate onto striatal spiny projection neurons and cholinergic interneurons. Some dopaminergic axon terminals release GABA. Glutamate release by DA neurons has a developmental role, facilitating axonal growth and survival, and may determine in part the critical contribution of the ventral striatum to psychostimulant-induced behavior. Vesicular glutamate coentry may have synergistic effects on vesicular DA filling. The multilingual transmission of DA neurons across multiple striatal domains and the increasing insight into the role of glutamate cotransmission in the ventral striatum highlight the importance of analyzing DA neuron transmission at the synaptic level. C1 [Trudeau, Louis-Eric] Univ Montreal, Fac Med, Neurosci Res Grp, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada. [Trudeau, Louis-Eric] Univ Montreal, Fac Med, Neurosci Res Grp, Dept Neurosci, Montreal, PQ H3C 3J7, Canada. [Hnasko, Thomas S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Wallen-Mackenzie, Asa] Uppsala Univ, Dept Neurosci, Unit Funct Neurobiol, Uppsala, Sweden. [Morales, Marisela] NIDA, Intramural Res Program, Neuronal Networks Sect, Baltimore, MD USA. [Rayport, Steven; Sulzer, David] Columbia Univ, Dept Psychiat, New York, NY USA. [Rayport, Steven; Sulzer, David] NYS Psychiat Inst, Dept Mol Therapeut, New York, NY USA. [Sulzer, David] Columbia Univ, Dept Neurol, New York, NY USA. [Sulzer, David] Columbia Univ, Dept Pharmacol, New York, NY USA. RP Trudeau, LE (reprint author), Univ Montreal, Fac Med, Neurosci Res Grp, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada. EM louis-eric.trudeau@umontreal.ca RI Diana, Marco/D-1475-2011; Wallen-Mackenzie, Asa/B-9105-2017 OI Diana, Marco/0000-0002-6561-5642; Wallen-Mackenzie, Asa/0000-0002-8713-070X FU Medical Research Council [MOP-106556]; NIDA NIH HHS [R01 DA007418, K01 DA026504, R01 DA017978]; NIMH NIH HHS [P50 MH086404] NR 124 TC 23 Z9 23 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-63427-6; 978-0-444-63425-2 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2014 VL 211 BP 141 EP 164 DI 10.1016/B978-0-444-63425-2.00006-4 PG 24 WC Neurosciences SC Neurosciences & Neurology GA BB1VO UT WOS:000341413700007 PM 24968779 ER PT S AU Chlanda, P Sachse, M AF Chlanda, Petr Sachse, Martin BE Kuo, J TI Cryo-electron Microscopy of Vitreous Sections SO ELECTRON MICROSCOPY: METHODS AND PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cryo-ultramicrotomy; Cryo-transfer; Cryo-transmission electron microscopy; Trimming; Sectioning; Vitrification ID ELECTRON TOMOGRAPHY; TISSUE-SECTIONS; WATER; VITRIFICATION; CELLS AB More than 30 years ago two groups independently reported the vitrification of pure water, which was until then regarded as impossible without a cryoprotectant [1, 2]. This opened the opportunity to cryo-electron microscopy (cryo-EM) to observe biological samples at nanometer scale, close to their native state. However, poor electron penetration through biological samples sets the limit for sample thickness to less than the average size of the mammalian cell. In order to image bulky specimens at the cell or tissue level in transmission electron microscopy (TEM), a sample has to be either thinned by focused ion beam or mechanically sectioned. The latter technique, Cryo-Electron Microscopy of Vitreous Section (CEMOVIS), employs cryo-ultramicrotomy to produce sections with thicknesses of 40-100 mu m of vitreous biological material suitable for cryo-EM. CEMOVIS consists of trimming and sectioning a sample with a diamond knife, placing and attaching the section onto an electron microscopy grid, transferring the grid to the cryo-electron microscope and imaging. All steps must be carried on below devitrification temperature to obtain successful results. In this chapter we provide a step-by-step guide to produce and image vitreous sections of a biological sample. C1 [Chlanda, Petr] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Sachse, Martin] Leibniz Inst Mol Pharmakol Forsch Verbund, Berlin, Germany. RP Chlanda, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. NR 22 TC 6 Z9 6 U1 2 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-776-1; 978-1-62703-775-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1117 BP 193 EP 214 DI 10.1007/978-1-62703-776-1_10 D2 10.1007/978-1-62703-776-1 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Microscopy SC Biochemistry & Molecular Biology; Microscopy GA BB1KV UT WOS:000341167200011 PM 24357365 ER PT J AU Hyodo, F Krishna, MC Mitchell, JB Utsumi, H AF Hyodo, Fuminori Krishna, Murali C. Mitchell, J. B. Utsumi, Hideo TI In vivo tumor redox imaging using magnetic resonance imaging SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Hyodo, Fuminori; Utsumi, Hideo] Kyushu Univ, Innovat Ctr Med Redox Nav, Fukuoka 812, Japan. [Hyodo, Fuminori] JST, CREST, Chiyoda Ku, Tokyo, Japan. [Krishna, Murali C.; Mitchell, J. B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM hyodof@redoxnavi.med.kyushu-u.ac.jp NR 3 TC 0 Z9 0 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2014 VL 34 SU 1 MA 533 BP S113 EP S113 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO3ZM UT WOS:000341276000434 ER PT J AU Gamaldo, AA Gamaldo, CE Allaire, JC Aiken-Morgan, AT Salas, RE Szanton, S Whitfield, KE AF Gamaldo, Alyssa A. Gamaldo, Charlene E. Allaire, Jason C. Aiken-Morgan, Adrienne T. Salas, Rachel E. Szanton, Sarah Whitfield, Keith E. TI Sleep Complaints in Older Blacks: Do Demographic and Health Indices Explain Poor Sleep Quality and Duration? SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep quality; sleep duration; demographics; health; Blacks ID LIFE-COURSE; CES-D; CARDIOVASCULAR-DISEASE; CUMULATIVE ADVANTAGE; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; FOUNDATION SLEEP; FINANCIAL STRAIN; NATIONAL-HEALTH; US ADULTS AB Objective: To examine the relationship between measures of sleep quality and the presence of commonly encountered comorbid and sociodemographic conditions in elderly Black subjects. Method: Analyses included participants from the Baltimore Study of Black Aging (BSBA; n = 450; mean age 71.43 years; SD 9.21). Pittsburgh Sleep Quality Index (PSQI) measured overall sleep pattern and quality. Self-reported and objective measures of physical and mental health data and demographic information were collected for all participants. Results: Sociodemographic and comorbid health factors were significantly associated with sleep quality. Results from regression analyses revealed that older age, current financial strain, interpersonal problems, and stress were unique predictors of worse sleep quality. Sleep duration was significantly correlated with age, depressive affect, interpersonal problems, and stress; only age was a unique signifi cant predictor. While participants 62 years or younger had worse sleep quality with increasing levels of stress, there was no signifi cant relationship between sleep quality and stress for participants 81 years and older. Conclusions: Several potential mechanisms may explain poor sleep in urban, community dwelling Blacks. Perceived stressors, including current financial hardship or hardship experienced for an extended time period throughout the lifespan, may influence sleep later in life. C1 [Gamaldo, Alyssa A.] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [Gamaldo, Alyssa A.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Gamaldo, Charlene E.; Salas, Rachel E.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Allaire, Jason C.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Aiken-Morgan, Adrienne T.; Whitfield, Keith E.] Duke Univ, Ctr Biobehav Hlth Dispar, Durham, NC USA. [Szanton, Sarah] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Whitfield, Keith E.] Duke Univ, Durham, NC USA. RP Gamaldo, AA (reprint author), NIA, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Alyssa.Gamaldo@nih.gov FU National Institute on Aging (NIA) [R01 AG24108, AG24108-S1, T32 AG000029]; Intramural Research Program of the NIH, National Institute on Aging FX This was not an industry supported study. The authors have indicated no financial conflicts of interest. The data for this paper came from a project supported by the National Institute on Aging (NIA; R01 AG24108 and AG24108-S1) to Dr. Whitfield. Dr. Aiken-Morgan is supported by T32 AG000029 from the NIA. This research was also supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 49 TC 4 Z9 4 U1 1 U2 7 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 7 BP 725 EP 731 DI 10.5664/jcsm.3858 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AO2GN UT WOS:000341136100004 PM 25024649 ER PT J AU Chatterjee, AG Esnault, C Guo, YB Hung, S McQueen, PG Levin, HL AF Chatterjee, Atreyi Ghatak Esnault, Caroline Guo, Yabin Hung, Stevephen McQueen, Philip G. Levin, Henry L. TI Serial number tagging reveals a prominent sequence preference of retrotransposon integration SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LEUKEMIA-VIRUS INTEGRATION; GENE-THERAPY; REVERSE TRANSCRIPTION; SCHIZOSACCHAROMYCES-POMBE; CONSENSUS SEQUENCES; HIV-1 INTEGRATION; DNA INTEGRATION; SITE SELECTION; HUMAN GENOME; TF1 AB Transposable elements (TE) have both negative and positive impact on the biology of their host. As a result, a balance is struck between the host and the TE that relies on directing integration to specific genome territories. The extraordinary capacity of DNA sequencing can create ultra dense maps of integration that are being used to study the mechanisms that position integration. Unfortunately, the great increase in the numbers of insertion sites detected comes with the cost of not knowing which positions are rare targets and which sustain high numbers of insertions. To address this problem we developed the serial number system, a TE tagging method that measures the frequency of integration at single nucleotide positions. We sequenced 1 million insertions of retrotransposon Tf1 in the genome of Schizosaccharomyces pombe and obtained the first profile of integration with frequencies for each individual position. Integration levels at individual nucleotides varied over two orders of magnitude and revealed that sequence recognition plays a key role in positioning integration. The serial number system is a general method that can be applied to determine precise integration maps for retroviruses and gene therapy vectors. C1 [Chatterjee, Atreyi Ghatak; Esnault, Caroline; Guo, Yabin; Hung, Stevephen; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. [McQueen, Philip G.] NIH, Math & Stat Comp Lab, Div Computat, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. EM henrylevin@nih.gov RI Esnault, Caroline/C-7221-2015; OI , Guo/0000-0001-8316-8527 FU Intramural Research Program of the National Institutes of Health (NIH) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Intramural Research Program of the NIH, Center for Information Technology FX Intramural Research Program of the National Institutes of Health (NIH) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Intramural Research Program of the NIH, Center for Information Technology [to P.G.M.]. Source of open access funding: Publication charges will be paid by the Intramural Research Program of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 34 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 13 BP 8449 EP 8460 DI 10.1093/nar/gku534 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7ER UT WOS:000341515400029 PM 24948612 ER PT J AU Ghosh, A Jindal, S Bentley, AA Hinnebusch, AG Komar, AA AF Ghosh, Arnab Jindal, Supriya Bentley, Amber A. Hinnebusch, Alan G. Komar, Anton A. TI Rps5-Rps16 communication is essential for efficient translation initiation in yeast S-cerevisiae SO NUCLEIC ACIDS RESEARCH LA English DT Article ID START CODON SELECTION; RIBOSOMAL-PROTEIN S5; FACTOR 1 EIF1; EUKARYOTIC RIBOSOME; PREINITIATION COMPLEX; MODULATES AUTOREGULATION; AUG RECOGNITION; SITE SELECTION; GTP HYDROLYSIS; IN-VIVO AB Conserved ribosomal proteins frequently harbor additional segments in eukaryotes not found in bacteria, which could facilitate eukaryotic-specific reactions in the initiation phase of protein synthesis. Here we provide evidence showing that truncation of the N-terminal domain (NTD) of yeast Rps5 (absent in bacterial ortholog S7) impairs translation initiation, cell growth and induction of GCN4 mRNA translation in a manner suggesting incomplete assembly of 48S preinitiation complexes (PICs) at upstream AUG codons in GCN4 mRNA. Rps5 mutations evoke accumulation of factors on native 40S subunits normally released on conversion of 48S PICs to 80S initiation complexes (ICs) and this abnormality and related phenotypes are mitigated by the SUI5 variant of eIF5. Remarkably, similar effects are observed by substitution of Lys45 in the Rps5-NTD, involved in contact with Rps16, and by eliminating the last two residues of the C-terminal tail (CTT) of Rps16, believed to contact initiator tRNA base-paired to AUG in the P site. We propose that Rps5-NTD-Rps16-NTD interaction modulates Rps16-CTT association with Met-tRNA(i)(Met) to promote a functional 48S PIC. C1 [Ghosh, Arnab; Jindal, Supriya; Bentley, Amber A.; Komar, Anton A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. [Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Komar, AA (reprint author), Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. EM a.komar@csuohio.edu OI GHOSH, ARNAB/0000-0003-1952-1044 FU Human Frontiers Science Program (HFSP) [RGP0024]; Ohio Scholars Program; Cleveland State University Doctoral Dissertation Research Expense Award; Center for Gene Regulation in Health and Disease (GRHD) at Cleveland State University; Intramural Program of the National Institutes of Health FX Human Frontiers Science Program (HFSP) [RGP0024 to A.A.K.]; Ohio Scholars Program [to A.A.K.]; Cleveland State University Doctoral Dissertation Research Expense Award [to A.G.]; Center for Gene Regulation in Health and Disease (GRHD) at Cleveland State University [to A.A.K.], and the Intramural Program of the National Institutes of Health [to A.G.H.]. Funding for open access charge: HFSP [RGP0024]. NR 59 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 13 BP 8537 EP 8555 DI 10.1093/nar/gku550 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7ER UT WOS:000341515400036 PM 24948608 ER PT J AU Wu, QJ Wang, J Gao, J Zhang, W Han, LH Gao, S Gao, YT Ji, BT Zheng, W Shu, XO Xiang, YB AF Wu, Qi-Jun Wang, Jing Gao, Jing Zhang, Wei Han, Li-Hua Gao, Shan Gao, Yu-Tang Ji, Bu-Tian Zheng, Wei Shu, Xiao-Ou Xiang, Yong-Bing TI Urinary Isothiocyanates Level and Liver Cancer Risk: A Nested Case-Control Study in Shanghai, China SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID CRUCIFEROUS VEGETABLES INTAKE; S-TRANSFERASE M1; FACTOR-KAPPA-B; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; T1 POLYMORPHISMS; BREAST-CANCER; MENS HEALTH; METAANALYSIS AB Experimental studies have provided evidence that isothiocyanates (ITCs) from cruciferous vegetables may modulate carcinogen metabolism and facilitate carcinogen detoxification and reduce cancer risk. However, no epidemiological studies on liver cancer were reported. This study investigates the association between urinary ITCs levels and liver cancer risk among men and women in Shanghai, China. A nested case-control study of 217 incident cases of liver cancer and 427 matched controls identified from the Shanghai Women's Health Study and Shanghai Men's Health Study was conducted. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) summarizing the association between urinary ITCs levels and liver cancer risk. Compared to those with undetectable ITCs, nonsignificantly inverse association was observed among detectable (OR = 0.80; 95% CI = 0.51-1.26), below-median (OR D 0.76; 95% CI = 0.47-1.24), and above-median concentration (OR = 0.86; 95% CI = 0.52-1.41) with liver cancer risk. Similar patterns were observed when urinary ITCs levels were categorized into tertiles or quartiles. Although our study firstly focused on the association between urinary ITCs exposure and liver cancer risk, we did not find significant results. Future multicenter prospective, different population studies are warranted to validate our findings. C1 [Wu, Qi-Jun; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogene & Related Genes, Shanghai Canc Inst,Renji Hosp, Shanghai 200032, Peoples R China. [Wu, Qi-Jun; Wang, Jing; Gao, Jing; Zhang, Wei; Han, Li-Hua; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Dept Epidemiol, Shanghai Canc Inst,Renji Hosp, Shanghai 200032, Peoples R China. [Gao, Shan] Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Management, Zhengzhou 450052, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, 25,Lane 2200,Xie Tu Rd, Shanghai 200032, Peoples R China. EM ybxiang@shsci.org FU State Key Project Specialized for Infectious Diseases of China [2008ZX10002-015, 2012ZX10002008-002]; Shanghai Municipal Bureau of Public Health [2008208, 2008144]; U.S. National Institutes of Health [R37 CA070867, R01 CA82729] FX This work was supported by funds from the State Key Project Specialized for Infectious Diseases of China (Nos. 2008ZX10002-015 and 2012ZX10002008-002 to Yong- Bing Xiang), research funds of the Shanghai Municipal Bureau of Public Health (No. 2008208 to Jing Gao, 2008144 to Wei Zhang), as well as grants (R37 CA070867 to Wei Zheng, R01 CA82729 to XO Shu) from the U.S. National Institutes of Health for the parent studies. NR 42 TC 1 Z9 1 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PY 2014 VL 66 IS 6 BP 1023 EP 1029 DI 10.1080/01635581.2014.936953 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA AO5UJ UT WOS:000341410500014 PM 25076394 ER PT S AU Jee, YH Baron, J Phillip, M Bhutta, ZA AF Jee, Youn Hee Baron, Jeffrey Phillip, Moshe Bhutta, Zulfiqar A. BE Koletzko, B Shamir, R Turck, D Phillip, M TI Malnutrition and Catch-Up Growth during Childhood and Puberty SO NUTRITION AND GROWTH: YEARBOOK 2014 SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID MIDDLE-INCOME COUNTRIES; LINEAR GROWTH; ADULT HEALTH; UNDERNUTRITION; PRETERM C1 [Jee, Youn Hee; Baron, Jeffrey] NICHHD, NIH, Bethesda, MD 20892 USA. [Phillip, Moshe] Natl Ctr Childhood Diabet, Schneider Childrens Med Ctr Israel, Jesse Z & Sara Lea Shafer Inst Endocrinol & Diabe, IL-4920235 Petah Tiqwa, Israel. [Phillip, Moshe] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Bhutta, Zulfiqar A.] Sick Kids Ctr Global Child Hlth, Robert Harding Chair Global Child Hlth & Policy, Toronto, ON, Canada. [Bhutta, Zulfiqar A.] Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan. RP Jee, YH (reprint author), NICHHD, NIH, CRC Room 1-3330 10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM youn.jee@nih.gov; baronj@cc1.nichd.nih.gov; mosheph@post.tau.ac.il; zulfiqar.bhutta@aku.edu FU Intramural NIH HHS [Z01 HD000640-13] NR 10 TC 1 Z9 1 U1 1 U2 5 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-318-02566-8; 978-3-318-02565-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2014 VL 109 BP 89 EP 100 DI 10.1159/000356109 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BB1LR UT WOS:000341188800006 PM 24457569 ER PT J AU Li, FY Cheng, KJ Antoline, JFG Iyer, MR Matyas, GR Torres, OB Jalah, R Beck, Z Alving, CR Parrish, DA Deschamps, JR Jacobson, AE Rice, KC AF Li, Fuying Cheng, Kejun Antoline, Joshua F. G. Iyer, Malliga R. Matyas, Gary R. Torres, Oscar B. Jalah, Rashmi Beck, Zoltan Alving, Carl R. Parrish, Damon A. Deschamps, Jeffrey R. Jacobson, Arthur E. Rice, Kenner C. TI Synthesis and immunological effects of heroin vaccines SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID OXIDE-BRIDGED PHENYLMORPHANS; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; MORPHINE CONJUGATE VACCINE; N-PHENETHYL ANALOGS; SERUM-ALBUMIN; ANTIBODIES; HAPTEN; RATS; DERIVATIVES; OXYCODONE AB Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A "classical" opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acetylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens. C1 [Li, Fuying; Cheng, Kejun; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Li, Fuying; Cheng, Kejun; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Matyas, Gary R.; Torres, Oscar B.; Jalah, Rashmi; Beck, Zoltan; Alving, Carl R.] Walter Reed Army Inst Res, Lab Adjuvant & Antigen Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Torres, Oscar B.; Jalah, Rashmi; Beck, Zoltan] Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program, Bethesda, MD 20817 USA. [Parrish, Damon A.; Deschamps, Jeffrey R.] Naval Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM kenner.rice@nih.gov FU NIH Intramural Research Program of National Institute on Drug Abuse; NIH Intramural Research Program of National Institute of Alcohol Abuse and Alcoholism; Henry M. Jackson Foundation for the Advancement of Military Medicine [W81XWH-07-2-067]; U.S. Army Medical Research and Materiel Command (MRMC) [W81XWH-07-2-067]; National Institute on Drug Abuse (NIH) [1DP1DA034787-01]; NIDA [Y1-DA1101]; Naval Research Laboratory (NRL) FX The work of FL, KC, JFGA, MRI, AEJ, and KCR was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism, The work of GRM, OBT, RJ, ZB, and CRA was supported through a Cooperative Agreement Award (no. W81XWH-07-2-067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Army Medical Research and Materiel Command (MRMC). The work was partially supported by an Avant Garde award to GRM from the National Institute on Drug Abuse (NIH grant no. 1DP1DA034787-01). The X-ray crystallographic work was supported by NIDA through an Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). NIH, DHHS. Ms. Elaine Morrison, and Mr Marcus Gallon provided outstanding technical assistance. We thank Noel Whittaker and Dr John Lloyd (Mass Spectrometry Facility, NIDDK) for the mass spectral data, and Drs Klaus Gawrisch and Walter Teague (Laboratory of Membrane Biochemistry and Biophysics, NIAAA) for NMR spectroscopic data. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adhered to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 1996 edition. The views expressed in this article are those of the authors and do not necessarily reflect the official policy of the Department of the Army, Department of Defense, or NIH, or the U.S. Government. NR 41 TC 5 Z9 5 U1 1 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2014 VL 12 IS 37 BP 7211 EP 7232 DI 10.1039/c4ob01053a PG 22 WC Chemistry, Organic SC Chemistry GA AO5CU UT WOS:000341360400005 PM 24995943 ER PT B AU Hamilton, HE Chou, WYS AF Hamilton, Heidi E. Chou, Wen-ying Sylvia BE Hamilton, HE Chou, WYS TI Health communication as applied linguistics Introduction SO ROUTLEDGE HANDBOOK OF LANGUAGE AND HEALTH COMMUNICATION SE Routledge Handbooks in Applied Linguistics LA English DT Editorial Material; Book Chapter ID CHALLENGES; IDENTITY C1 [Hamilton, Heidi E.] Georgetown Univ, Dept Linguist, Washington, DC 20057 USA. [Hamilton, Heidi E.] Univ Innsbruck, A-6020 Innsbruck, Austria. [Hamilton, Heidi E.] Free Univ Berlin, Berlin, Germany. [Chou, Wen-ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Hamilton, HE (reprint author), Georgetown Univ, Dept Linguist, Washington, DC 20057 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85697-1; 978-0-415-67043-2 J9 ROUT HANDB APPL PY 2014 BP 1 EP 12 PG 12 WC Health Policy & Services; Linguistics SC Health Care Sciences & Services; Linguistics GA BB1JD UT WOS:000341147600001 ER PT B AU Prestin, A Chou, WYS AF Prestin, Abby Chou, Wen-ying Sylvia BE Hamilton, HE Chou, WYS TI Web 2.0 and the changing health communication environment SO ROUTLEDGE HANDBOOK OF LANGUAGE AND HEALTH COMMUNICATION SE Routledge Handbooks in Applied Linguistics LA English DT Article; Book Chapter ID NATIONAL TRENDS SURVEY; DIGITAL DIVIDE; BREAST-CANCER; SUPPORT GROUP; SOCIAL MEDIA; INFORMATION; INTERNET; ONLINE; FACEBOOK; YOUTUBE C1 [Prestin, Abby] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Chou, Wen-ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Prestin, A (reprint author), US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. NR 61 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85697-1; 978-0-415-67043-2 J9 ROUT HANDB APPL PY 2014 BP 184 EP 197 PG 14 WC Health Policy & Services; Linguistics SC Health Care Sciences & Services; Linguistics GA BB1JD UT WOS:000341147600013 ER PT B AU Davis, B Maclagan, M Shenk, D AF Davis, Boyd Maclagan, Margaret Shenk, Dena BE Hamilton, HE Chou, WYS TI Exploring communicative interactions between visitors and assisted-living residents with dementia SO ROUTLEDGE HANDBOOK OF LANGUAGE AND HEALTH COMMUNICATION SE Routledge Handbooks in Applied Linguistics LA English DT Article; Book Chapter ID LINGUISTIC ABILITY; COGNITIVE FUNCTION; NURSING-HOME; EARLY-LIFE; DISCOURSE; PEOPLE; CARE; NUN C1 [Davis, Boyd] UNC Charlotte, Charlotte, NC 28223 USA. [Davis, Boyd] NIH, Bethesda, MD USA. [Maclagan, Margaret] Univ Canterbury, Christchurch 1, New Zealand. [Shenk, Dena] UNC Charlotte, Gerontol Program, Charlotte, NC USA. RP Davis, B (reprint author), UNC Charlotte, Charlotte, NC 28223 USA. NR 54 TC 2 Z9 2 U1 0 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85697-1; 978-0-415-67043-2 J9 ROUT HANDB APPL PY 2014 BP 344 EP 361 PG 18 WC Health Policy & Services; Linguistics SC Health Care Sciences & Services; Linguistics GA BB1JD UT WOS:000341147600022 ER PT S AU Holmberg, KV Hoffman, MP AF Holmberg, Kyle V. Hoffman, Matthew P. BE Ligtenberg, AJM Veerman, ECI TI Anatomy, Biogenesis and Regeneration of Salivary Glands SO SALIVA: SECRETION AND FUNCTIONS SE Monographs in Oral Science LA English DT Article; Book Chapter ID ADENOVIRAL-MEDIATED TRANSFER; GROWTH-FACTOR RECEPTOR; RAT PAROTID-GLANDS; SUBMANDIBULAR-GLAND; BRANCHING MORPHOGENESIS; PROGENITOR CELLS; NECK-CANCER; PARASYMPATHETIC INNERVATION; TRANSCRIPTION FACTOR; PANCREATIC LINEAGES AB An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients each year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland, which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting that nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of 3 general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. (C) 2014 S. Karger AG, Basel C1 [Holmberg, Kyle V.; Hoffman, Matthew P.] NIDCR, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), NIDCR, NIH, Bldg 30 Rm 433,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM drkyle.holmberg@gmail.com; mhoffman@mail.nih.gov FU Intramural NIH HHS [Z99 DE999999, ZIA DE000707-10, ZIA DE000722-06] NR 76 TC 15 Z9 15 U1 1 U2 12 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0077-0892 BN 978-3-318-02596-5; 978-3-318-02595-8 J9 MONOGR ORAL SCI JI Monogr. Oral Sci. PY 2014 VL 24 BP 1 EP 13 DI 10.1159/000358776 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BB1TU UT WOS:000341360500002 PM 24862590 ER PT J AU Field, D Sterk, P Kottmann, R De Smet, JW Amaral-Zettler, L Cochrane, G Cole, JR Davies, N Dawyndt, P Garrity, GM Gilbert, JA Glockner, FO Hirschman, L Klenk, HP Knight, R Kyrpides, N Meyer, F Karsch-Mizrachi, I Morrison, N Robbins, R San Gil, I Sansone, S Schriml, L Tatusova, T Ussery, D Yilmaz, P White, O Wooley, J Caporaso, G AF Field, Dawn Sterk, Peter Kottmann, Renzo De Smet, J. Wim Amaral-Zettler, Linda Cochrane, Guy Cole, James R. Davies, Neil Dawyndt, Peter Garrity, George M. Gilbert, Jack A. Gloeckner, Frank Oliver Hirschman, Lynette Klenk, Hans-Peter Knight, Rob Kyrpides, Nikos Meyer, Folker Karsch-Mizrachi, Ilene Morrison, Norman Robbins, Robert San Gil, Inigo Sansone, Susanna Schriml, Lynn Tatusova, Tatiana Ussery, Dave Yilmaz, Pelin White, Owen Wooley, John Caporaso, Gregory TI Genomic Standards Consortium Projects SO STANDARDS IN GENOMIC SCIENCES LA English DT Article ID MINIMUM INFORMATION AB The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities. Copyright (C) retained by original authors C1 [Field, Dawn] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England. [Field, Dawn; Sterk, Peter; Sansone, Susanna] Univ Oxford, Oxford e Res Ctr, Oxford, England. [Kottmann, Renzo; Gloeckner, Frank Oliver; Yilmaz, Pelin] Bremen & Jacobs Univ Bremen, Max Planck Inst Marine Microbiol, Microbial Genom Grp, Bremen, Germany. [De Smet, J. Wim; Dawyndt, Peter] Univ Ghent, Dept Appl Math & Comp Sci, B-9000 Ghent, Belgium. [Amaral-Zettler, Linda] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Cochrane, Guy] European Bioinformat Inst, European Mol Biol Lab EMBL Outstn, Cambridge, England. [Cole, James R.] Michigan State Univ, Ctr Microbial Ecol, E Lansing, MI 48824 USA. [Davies, Neil] Univ Calif Berkeley, Gump South Pacific Res Stn, Moorea, Fr Polynesia. [Davies, Neil] Univ Oxford, Dept Zool, Biodivers Inst, Oxford OX1 3PS, England. [Garrity, George M.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Gilbert, Jack A.; Meyer, Folker] Argonne Natl Lab, Inst Genom & Syst Biol, Argonne, IL 60439 USA. [Gilbert, Jack A.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Hirschman, Lynette] Mitre Corp, Ctr Informat Technol, Bedford, MA 01730 USA. [Klenk, Hans-Peter] DSMZ German Collect Microorganisms & Cell Culture, Braunschweig, Germany. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Kyrpides, Nikos] DOE Joint Genome Inst, Walnut Creek, CA USA. [Meyer, Folker] Univ Chicago, Computat Inst, Chicago, IL 60637 USA. [Karsch-Mizrachi, Ilene; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Morrison, Norman] Univ Manchester, Manchester, Lancs, England. [Robbins, Robert; Wooley, John] Univ Calif San Diego, La Jolla, CA 92093 USA. [San Gil, Inigo] Univ New Mexico, Dept Biol, LTER Network Off, Albuquerque, NM 87131 USA. [Schriml, Lynn; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Ussery, Dave] DOE Oak Ridge Natl Lab, Oak Ridge, TN USA. [Caporaso, Gregory] No Arizona Univ, Ctr Microbial Genet & Genom, Flagstaff, AZ 86011 USA. RP Field, D (reprint author), Ctr Ecol & Hydrol, Maclean Bldg,Benson Lane, Wallingford OX10 8BB, Oxon, England. RI Knight, Rob/D-1299-2010; Davies, Neil/E-5863-2012; OI Dawyndt, Peter/0000-0002-1623-9070; Yilmaz, Pelin/0000-0003-4724-323X; Sterk, Peter/0000-0003-1668-7778; Davies, Neil/0000-0001-8085-5014; Cochrane, Guy/0000-0001-7954-7057; Schriml, Lynn/0000-0001-8910-9851; Ussery, David/0000-0003-3632-5512; Kyrpides, Nikos/0000-0002-6131-0462 NR 3 TC 8 Z9 8 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2014 VL 9 IS 3 DI 10.4056/sigs.5559680 PG 3 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA AL2ZQ UT WOS:000338995000023 PM 25197446 ER PT B AU Rajczi, A AF Rajczi, Alex BE Allhoff, F Hall, M TI Fiscal Objections to Expanded Health Coverage A Case Study of the Affordable Care Act SO AFFORDABLE CARE ACT DECISION: PHILOSOPHICAL AND LEGAL IMPLICATIONS SE Routledge Studies in Contemporary Philosophy LA English DT Article; Book Chapter C1 [Rajczi, Alex] NIH, Dept Clin Bioeth, Bethesda, MD USA. RP Rajczi, A (reprint author), Claremont McKenna Coll, Claremont, CA 91711 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-315-88512-4; 978-0-415-71026-8 J9 ROUT STUD CONTEMP PH PY 2014 VL 57 BP 195 EP 208 PG 14 WC Health Policy & Services; Law SC Health Care Sciences & Services; Government & Law GA BB1II UT WOS:000341140800014 ER PT J AU Guo, XC Winkler, CA Li, J Guan, L Tang, MZ Liao, J Deng, H de The, G Zeng, Y O'Brien, SJ AF Guo, Xiuchan Winkler, Cheryl A. Li, Ji Guan, Li Tang, Minzhong Liao, Jian Deng, Hong de The, Guy Zeng, Yi O'Brien, Stephen J. TI Evaluation and Integration of Genetic Signature for Prediction Risk of Nasopharyngeal Carcinoma in Southern China SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID EPSTEIN-BARR-VIRUS; GENOME-WIDE ASSOCIATION; HLA CLASS-I; SUSCEPTIBILITY; INFECTION; POPULATION; EXPRESSION; LYMPHOMA; TAIWAN; REGION AB Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). Results. The reported associations between ITGA9 variants and NPC were not replicated. Multiple loci of GABBR1, HLA-F, HLA-A, and HCG9 were statistically significant in both cohorts (P-combined range from 5.96 x 10(-17) to 0.02). We show for the first time that these factors influence NPC development independent of environmental risk factors. This study also indicated that the SNP alone cannot serve as a predictive/diagnostic marker for NPC. Integrating the most significant SNP with IgA antibodies status to EBV, which is presently used as screening/diagnostic marker for NPC in Chinese populations, did not improve the AUC estimate for diagnosis of NPC. C1 [Guo, Xiuchan; Li, Ji] Wenzhou Med Univ, Sch Lab Med & Life Sci, Key Lab Lab Med, Wenzhou 325000, Peoples R China. [Guo, Xiuchan; Zeng, Yi] Chinese CDC, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing 10052, Peoples R China. [Guo, Xiuchan] ICF Int, Atlanta, GA 30329 USA. [Winkler, Cheryl A.] NCI, Basic Res Lab, Frederick Natl Lab, Leidos Biomed Res Inc, Frederick, MD 21702 USA. [Guan, Li; O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199004, Russia. [Tang, Minzhong; Zeng, Yi] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100022, Peoples R China. [Tang, Minzhong; Deng, Hong] Wuzhou Red Cross Hosp, Ctr Canc, Guangxi 543002, Peoples R China. [Liao, Jian] Cangwu Inst Nasopharyngeal Carcinoma Control & Pr, Wuzhou 543100, Guangxi, Peoples R China. [de The, Guy] Inst Pasteur, F-75724 Paris, France. RP Guo, XC (reprint author), Wenzhou Med Univ, Sch Lab Med & Life Sci, Key Lab Lab Med, Wenzhou 325000, Peoples R China. EM xiuchan88@yahoo.com; zengy@public.bta.net.cn FU National Cancer Institute, National Institutes of Health [HHSN26120080001E]; Center for Cancer Research; National Natural Science Foundation of China [30672377]; Zhejiang Provincial Top Key Discipline of Laboratory Medicine, Key Science and Technology Innovation Team of Zhejiang Province [2010R50048] FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. This Research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was supported in part by the National Natural Science Foundation of China, Grant no. 30672377 and Zhejiang Provincial Top Key Discipline of Laboratory Medicine, Key Science and Technology Innovation Team of Zhejiang Province (2010R50048). The authors thank all the participants in the cohorts. They thank Anna Satcher Johnson for reviewing and editing the paper; Xinjian Zhang, Randall Johnson, and James Lautenberger for statistical advice; and Michael Malasky and Mary J. McNally for excellent technical assistance. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. NR 34 TC 2 Z9 2 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 434072 DI 10.1155/2014/434072 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AN7DN UT WOS:000340759100001 ER PT J AU Hashkes, PJ Spalding, SJ Hajj-Ali, R Giannini, EH Johnson, A Barron, KS Weisman, MH Pashinian, N Reiff, AO Samuels, J Wright, D Lovell, DJ Huang, B AF Hashkes, Philip J. Spalding, Steven J. Hajj-Ali, Rula Giannini, Edward H. Johnson, Anne Barron, Karyl S. Weisman, Michael H. Pashinian, Noune Reiff, Andreas O. Samuels, Jonathan Wright, Dowain Lovell, Daniel J. Huang, Bin TI The Effect of Rilonacept versus Placebo on Health-Related Quality of Life in Patients with Poorly Controlled Familial Mediterranean Fever SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID DOUBLE-BLIND; COLCHICINE; TRIAL; FIBROMYALGIA; FREQUENCY; CHILDREN; ATTACKS; GENE AB Objective. To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). Methods. As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. Results. Fourteen subjects were randomized; mean age was 24.4 +/- 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 +/- 49.5) but the psychosocial score was similar to the population norm (49.5 +/- 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 +/- 16.4 versus 23.7 +/- 14.5, P = 0.021) but not psychosocial scores (51.4 +/- 10.3 versus 49.8 +/- 12.4, P = 0.42). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. Conclusion. Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. C1 [Hashkes, Philip J.; Spalding, Steven J.; Hajj-Ali, Rula] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hashkes, Philip J.] Shaare Zedek Med Ctr, Pediat Rheumatol Unit, IL-91031 Jerusalem, Israel. [Giannini, Edward H.; Johnson, Anne; Lovell, Daniel J.; Huang, Bin] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Barron, Karyl S.] NIAID, Div Intramural Res, NIH, DHHS, Bethesda, MD 20892 USA. [Weisman, Michael H.; Pashinian, Noune] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Reiff, Andreas O.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Samuels, Jonathan] NYU, Langone Hosp Joint Dis, New York, NY 10003 USA. [Wright, Dowain] Childrens Hosp Cent Calif, Madera, CA 93636 USA. RP Hashkes, PJ (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM hashkesp@szmc.org.il RI Huang, bin/G-2468-2014; OI samuels, jonathan/0000-0002-1513-770X FU U.S. Food and Drug Administration, Office of Orphan Products Development [R01 FD003435]; Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Human Genome Research Institute; Cleveland Clinic Foundation FX This research was supported by the U.S. Food and Drug Administration, Office of Orphan Products Development (R01 FD003435). This trial was also supported by the Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Human Genome Research Institute, and the Cleveland Clinic Foundation. Rilonacept and placebo were supplied by Regeneron Pharmaceuticals. Target Health provided and partially subsidized the electronic data capture system and electronic database. NR 30 TC 1 Z9 1 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 854842 DI 10.1155/2014/854842 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AN7DR UT WOS:000340759500001 ER PT J AU Moreli, JB Santos, JH Rocha, CR Damasceno, DC Morceli, G Rudge, MV Bevilacqua, E Calderon, IMP AF Moreli, Jusciele Brogin Santos, Janine Hertzog Rocha, Clarissa Ribeiro Damasceno, Debora Cristina Morceli, Glilciane Rudge, Marilza Vieira Bevilacqua, Estela Paranhos Calderon, Iracema Mattos TI DNA Damage and Its Cellular Response in Mother and Fetus Exposed to Hyperglycemic Environment SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID GESTATIONAL-DIABETES-MELLITUS; ADVERSE PREGNANCY OUTCOMES; OXIDATIVE STRESS; CORD BLOOD; INTERNATIONAL ASSOCIATION; SIGNALING PATHWAYS; MITOCHONDRIAL-DNA; REPAIR MECHANISMS; CIGARETTE-SMOKE; CANCER AB The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA. C1 [Moreli, Jusciele Brogin; Damasceno, Debora Cristina; Morceli, Glilciane; Rudge, Marilza Vieira; Paranhos Calderon, Iracema Mattos] Sao Paulo State Univ, Grad Program Gynecol Obstet & Mastol, UNESP, Sao Paulo, Brazil. [Santos, Janine Hertzog] NIEHS, Mol Carcinogenesis Lab, Durham, NC USA. [Rocha, Clarissa Ribeiro] Univ Sao Paulo, Dept Microbiol, BR-05508 Sao Paulo, Brazil. [Bevilacqua, Estela] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo, Brazil. [Paranhos Calderon, Iracema Mattos] Sao Paulo State Univ, Botucatu Med Sch, Dept Obstet & Gynecol, UNESP, BR-18618000 Botucatu, SP, Brazil. RP Calderon, IMP (reprint author), Sao Paulo State Univ, Grad Program Gynecol Obstet & Mastol, UNESP, Sao Paulo, Brazil. EM calderon@fmb.unesp.br RI Morceli, Glilciane/C-7487-2012; Rocha, Clarissa/O-8946-2015; Rudge, Marilza /C-8338-2012; Bevilacqua, Estela/H-3354-2011; FAPESP, CDMF/J-3591-2015 OI Morceli, Glilciane/0000-0001-8216-9931; Rudge, Marilza /0000-0002-9227-832X; Bevilacqua, Estela/0000-0003-4178-4625; FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/18240-2, 2011/13562-1, 2012/23296-0] FX The authors acknowledge Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (Grant no. 2011/18240-2, 2011/13562-1, and 2012/23296-0). The authors would like to thank Carlos Frederico Martins Menck for scientific support. NR 85 TC 6 Z9 6 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 676758 DI 10.1155/2014/676758 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AN7BJ UT WOS:000340753200001 ER PT J AU Shen, XX An, YL Zhang, P Wang, JP Gregg, EW Zhang, B Li, H Gong, QH Chen, YY Xing, XY Engelgau, M Hu, YH Bennett, PH Li, GW AF Shen, Xiaoxia An, Yali Zhang, Ping Wang, Jinping Gregg, Edward W. Zhang, Bo Li, Hui Gong, Qiuhong Chen, Yanyan Xing, Xiaoyan Engelgau, Michael Hu, Yinghua Bennett, Peter H. Li, Guangwei TI Both Fasting and 2-hour post load glycemic progression predicts subsequent cardiovascular events in persons with impaired glucose tolerance: 23-year follow-up of the Da Qing diabetes prevention study SO CARDIOLOGY LA English DT Meeting Abstract C1 [Shen, Xiaoxia; An, Yali; Gong, Qiuhong; Chen, Yanyan; Li, Guangwei] Fuwai Hosp, Ctr Endocrinol & Cardiovasc Dis, Beijing, Peoples R China. [Zhang, Ping; Gregg, Edward W.; Engelgau, Michael] CDC, Div Diabet Translat, Atlanta, GA 30333 USA. [Wang, Jinping; Li, Hui; Hu, Yinghua] Da Qing First Hosp, Dept Cardiol, Da Qing, Peoples R China. [Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. [Zhang, Bo; Xing, Xiaoyan; Li, Guangwei] China Japan Friendship Hosp, Dept Endocrinol, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 129 SU 1 BP 11 EP 11 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO2PY UT WOS:000341168900030 ER PT J AU Ain, QU Greig, NH Nawaz, MS Rashid, S Kamal, MA AF Ain, Qurrat Ul Greig, Nigel H. Nawaz, Muhammad S. Rashid, Sajid Kamal, Mohammad A. TI Exploring N-1-p-Fluorobenzyl-Cymserine as an Inhibitor of 5-Lipoxygenase as a Candidate for Type 2 Diabetes and Neurodegenerative Disorder Treatment SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE -lipoxygenase; docking; fluorobenzylcymserine; 5type 2 diabetes ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; ASSOCIATION; MELLITUS; BRAIN; RISK; BUTYRYLCHOLINESTERASE; NEUROINFLAMMATION; DETERMINANTS; RESISTANCE AB Developing a single selective ligand to a target relevant to two mechanistically interlinked diseases, such as type 2 diabetes mellitus (T2DM) and a neurodegenerative disorder, like Parkinson's disease or Alzheimer's disease, provides the potential for an effective treatment that may impact both. The enzyme 5-lipoxygenase (5-LOX) has been revealed responsible for producing fatty acid molecules, leukotrienes. These leukotrienes are known to produce inflammatory responses in asthma and allergic reactions, to induce a reduction of tyrosine hydroxylase in brain, and are involved in the development of cardiac strokes, obesity and type 2 diabetes. N1-p-fluorobenzyl-cymserine (FBC), an analogue of cymserine and a known cholineterase inhibitor, was evaluated for inhibition of pleiotropic 5-LOX in our study. The stable 3D structure of 5-LOX was obtained from the Protein Data Bank (PDB) database and was implied for homology modeling of four reported mutant models. Each generated model was submitted to the Protein Model Database (PMDB) and employed for measuring inhibition and ligand efficiency of FBC with support of molecular docking. For each model, normal as well as mutant, FBC yielded remarkable inhibition constant values, with exothermic free binding energies. The current study revealed a highly reactive narrow fissure near the non-heme iron binding pocket of 5-LOX that contains residues crucial for 5-LOX stability and FBC binding. Investigating the binding of FBC with stabilized and destabilized 5-LOX structures confirmed it as a candidate therapeutic inhibitor worthy of assessment in preclinical models of T2DM and neurodegeneration. C1 [Ain, Qurrat Ul; Nawaz, Muhammad S.] COMSATS Inst Informat Technol, Dept Biosci, Islamabad, Pakistan. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Rashid, Sajid] Quaid I Azam Univ, Natl Ctr Bioinformat, Islamabad, Pakistan. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Fundamental & Appl Biol Grp, Metabol & Enzymol Unit, Jeddah 21589, Saudi Arabia. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM Greign@grc.nia.nih.gov; makamals@gmail.com OI Kamal, Mohammad Amjad/0000-0003-0088-0565 FU COMSATS Institute of Information Technology, Islamabad, Pakistan; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland, USA FX This research was supported in part by the COMSATS Institute of Information Technology, Islamabad, Pakistan, the King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia, and the Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland, USA. NR 36 TC 1 Z9 1 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 2 BP 197 EP 202 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AN8EL UT WOS:000340835800004 ER PT J AU Kamal, MA Priyamvada, S Anbazhagan, AN Jabir, NR Tabrez, S Greig, NH AF Kamal, Mohammad A. Priyamvada, Shubha Anbazhagan, Arivarasu N. Jabir, Nasimudeen R. Tabrez, Shams Greig, Nigel H. TI Linking Alzheimer's Disease and Type 2 Diabetes Mellitus via Aberrant Insulin Signaling and Inflammation SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Alzheimer's disease; Anti-cholinesterase; Butyrylcholinesterase; Inflammation; Type 2 diabetes mellitus ID GLYCATION END-PRODUCTS; GLUCAGON-LIKE PEPTIDE-1; NECROSIS-FACTOR-ALPHA; HUMAN SERUM BUTYRYLCHOLINESTERASE; AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR EXPRESSION; A-BETA LEVELS; MOUSE MODEL; METABOLIC SYNDROME; ANIMAL-MODELS AB Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two progressive and devastating health disorders afflicting millions of people worldwide. The probability and incidence of both have increased considerably in recent years consequent to increased longevity and population growth. Progressively more links are being continuously found between inflammation and central nervous system disorders like AD, Parkinson's disease, Huntington's disease, motor neuron disease, multiple sclerosis, stroke, traumatic brain injury and even cancers of the nervous tissue. The depth of the relationship depends on the timing and extent of anti- or pro-inflammatory gene expression. Inflammation has also been implicated in T2DM. Misfolding and fibrillization (of tissue specific and/or non-specific proteins) are features common to both AD and T2DM and are induced by as well as contribute to inflammation and stress (oxidative/glycation). This review appraises the roles of inflammation and abnormalities in the insulin signaling system as important shared features of T2DM and AD. The capacity of anti-cholinesterases in reducing the level of certain common inflammatory markers in particular if they may provide therapeutic potential to mitigate awry mechanisms leading to AD. C1 [Kamal, Mohammad A.; Jabir, Nasimudeen R.; Tabrez, Shams] King Abdulaziz Univ, King Fahd Med Res Ctr, Fundamental & Appl Biol Grp, Metabol & Enzymol Unit, Jeddah 21589, Saudi Arabia. [Priyamvada, Shubha; Anbazhagan, Arivarasu N.] Univ Illinois, Dept Med, Sect Digest Dis & Nutr, Chicago, IL 60612 USA. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Kamal, MA (reprint author), King Abdulaziz Univ, King Fahd Med Res Ctr, Fundamental & Appl Biol Grp, Metabol & Enzymol Unit, POB 80216, Jeddah 21589, Saudi Arabia. EM meu.fabg@hotmail.com RI Rehumathbeevi, Jabir/H-9483-2012; Tabrez, Shams/H-9476-2012 OI Rehumathbeevi, Jabir/0000-0001-8548-7986; Kamal, Mohammad Amjad/0000-0003-0088-0565; Tabrez, Shams/0000-0003-4550-415X FU Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois, Chicago, USA; deanship of scientific research at KSU [RGP-VPP-215] FX N.G. is supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. SP and NAA are grateful for support by the Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois, Chicago, USA. MAK, JNR and ST also extend their appreciation to the deanship of scientific research at KSU for funding the work through the research group project No- RGP-VPP-215. NR 140 TC 12 Z9 12 U1 0 U2 14 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 2 BP 338 EP 346 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AN8EL UT WOS:000340835800018 PM 24074448 ER PT J AU Reale, M Di Nicola, M Velluto, L D'Angelo, C Costantini, E Lahiri, DK Kamal, MA Yu, QS Greig, NH AF Reale, Marcella Di Nicola, Marta Velluto, Lucia D'Angelo, Chiara Costantini, Erica Lahiri, Debomoy K. Kamal, Mohammad A. Yu, Qian-sheng Greig, Nigel H. TI Selective Acetyl- and Butyrylcholinesterase Inhibitors Reduce Amyloid-beta Ex Vivo Activation of Peripheral Chemo-cytokines From Alzheimer's Disease Subjects: Exploring the Cholinergic Anti-inflammatory Pathway SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; inflammation; cytokines; amyloid-beta peptide (A beta); IL-1 beta; TNF-alpha; MCP-1; IL-6; IL-10; acetylcholinesterase (AChE); butyrylcholinesterase (BuChE); phenserine; cymserine; bisnorcymserine; phytohaemagglutinin (PHA) THP-1 cells; peripheral blood mononuclear cells (PBMCs); cholinesterase inhibitors ID BLOOD-BRAIN-BARRIER; NICOTINIC ACETYLCHOLINE-RECEPTOR; MATURE HIPPOCAMPAL-NEURONS; NECROSIS-FACTOR-ALPHA; A-BETA; SYSTEMIC INFLAMMATION; PRECURSOR PROTEIN; VAGUS NERVE; TNF-ALPHA; T-CELLS AB Increasing evidence suggests that elevated production and/or reduced clearance of amyloid-beta peptide (A beta) drives the early pathogenesis of Alzheimer's disease (AD). A beta soluble oligomers trigger a neurotoxic cascade that leads to neuronal dysfunction, neurodegeneration and, ultimately, clinical dementia. Inflammation, both within brain and systemically, together with a deficiency in the neurotransmitter acetylcholine (ACh) that underpinned the development of anticholinesterases for AD symptomatic treatment, are invariable hallmarks of the disease. The inter-relation between A beta, inflammation and cholinergic signaling is complex, with each feeding back onto the others to drive disease progression. To elucidate these interactions plasma samples and peripheral blood mononuclear cells (PBMCs) were evaluated from healthy controls (HC) and AD patients. Plasma levels of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and A beta were significantly elevated in AD vs. HC subjects, and ACh showed a trend towards reduced levels. A beta challenge of PBMCs induced a greater release of inflammatory cytokines interleukin-1 beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) from AD vs. HC subjects, with IL-10 being similarly affected. THP-1 monocytic cells, a cell culture counterpart of PBMCs and brain microglial cells, responded similarly to A beta as well as to phytohaemagglutinin (PHA) challenge, to allow preliminary analysis of the cellular and molecular pathways underpinning A beta-induced changes in cytokine expression. As amyloid-beta precursor protein expression, and hence A beta, has been reported regulated by particular cytokines and anticholinesterases, the latter were evaluated on A beta- and PHA-induced chemo-cytokine expression. Co-incubation with selective AChE/BuChE inhibitors, (-)-phenserine(AChE) and (-)-cymserine analogues (BuChE), mitigated the rise in cytokine levels and suggest that augmentation of the cholinergic anti-inflammatory pathway may prove valuable in AD. C1 [Reale, Marcella; D'Angelo, Chiara; Costantini, Erica] Univ G DAnnunzio, Dept Expt & Clin Sci, I-66123 Chieti, Italy. [Velluto, Lucia] Villa Serena Hosp, Citta SantAngelo Pescara, Italy. [Lahiri, Debomoy K.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. [Yu, Qian-sheng; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Reale, M (reprint author), Univ G DAnnunzio, NPD, Dept Expt & Clin Sci, Unit Immunodiagnost & Mol Pathol, Ed C,III Lev,Via Vestini 31, I-66123 Chieti, Italy. EM mreale@unich.it; greign@grc.nia.nih.gov OI DI NICOLA, MARTA/0000-0003-1748-1931 FU Italian MIUR; National Institute on Aging [AG18379, AG18884]; King Fahd Medical Research Center, King Abdulaziz University; National Institute on Aging, National Institutes of Health FX This work was supported by (i) grants from the Italian MIUR to M.R., (ii) the National Institute on Aging grants (AG18379 and AG18884) to D.K.L., (iii) the King Fahd Medical Research Center, King Abdulaziz University for M.A.K., and (iv) the Intramural Research Program, National Institute on Aging, National Institutes of Health for Q.S.Y. and N.H.G. The authors declare no conflicts of interest regarding the contents of this manuscript. NR 113 TC 9 Z9 10 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2014 VL 11 IS 6 BP 608 EP 622 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN9LF UT WOS:000340927400010 PM 24359497 ER PT J AU SanGiovanni, JP Rosen, R Kaushal, S AF SanGiovanni, J. P. Rosen, R. Kaushal, S. TI Application and Interpretation of Genome-Wide Association (GWA) Studies for Informing Pharmacogenomic Research - Examples from the Field of Age-Related Macular Degeneration SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Age-related macular degeneration; genome wide association; ligand; pharmacogenetic; pharmacogenomic; system; target ID RETINAL-PIGMENT EPITHELIUM; ACTIVATED PROTEIN-KINASES; ENDOTHELIAL GROWTH-FACTOR; DOPAMINE D-3 RECEPTOR; 3,000 SHARED CONTROLS; CHOROIDAL NEOVASCULARIZATION; HISTONE DEACETYLASE; PSYCHIATRIC-DISORDERS; INDUCED RETINOPATHY; GENETIC-VARIATION AB Genome-wide association (GWA) studies apply broad DNA scans on hundreds-of-thousands of common sequence variants in thousands of people for the purpose of mapping trait- or disease-related loci. We provide examples of ligand- and target-based studies from the field of age-related macular degeneration (AMD) to demonstrate the value of the GWA approach in confirmatory and exploratory pharmacogenomics research. Complementing this genomic analysis, we used a simple biochemical retinal pigment epithelium (RPE) oxidative, apoptotic high throughput screening (HTS) assay to identify compounds. This ligand-to-target-to DNA sequence variant-to disease approach provided guidance on rational design of preclinical studies and identified associations between: 1) valproic acid and advanced AMD-associated genes with the capacity to alter GABA-succinate signaling (ALDH5A1, CACNA1C, SUCLA2, and GABBR2) and chromatin remodeling (HDAC9); and 2) Ropinirole and a geographic atrophy-associated gene (DRD3) with the capacity to alter systems involved in cAMP-PKA signaling. In both applications of our method, the breadth of GWA findings allowed efficient expansion of results to identify enriched pathways and additional ligands capable of targeting pathway constituents. A disease associated SNP-to gene-to target-to ligand approach provided guidance to inform preventive and therapeutic preclinical studies investigating roles of targets in: 1) PPAR-RXR transcription complex constituents for neovascular AMD; and 2) the stress activated MAPK signaling cascade constituents for advanced AMD. Our conclusion is that publically available data from GWA studies can be used successfully with open-access genomics, proteomics, structural chemistry, and pharmacogenomics databases in an efficient, rational approach to streamline the processes of planning and implementation for confirmatory and exploratory pre-clinical studies of preventive or therapeutic pharmacologic treatments for complex diseases. C1 [SanGiovanni, J. P.] NEI, Bethesda, MD 20892 USA. [Rosen, R.] New York Eye & Ear Infirm, New York, NY 10009 USA. [Kaushal, S.] Retina Specialty Inst, Gainesville, FL 32605 USA. RP SanGiovanni, JP (reprint author), NEI, Bethesda, MD 20892 USA. EM jpsangio@post.harvard.edu FU NEI Intramural Research Program FX The data used for the original genetic analyses were obtained from the NEI Study of Age-Related Macular Degeneration (NEI-AMD) Database found at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs00 0182.v2.p1. We thank NEI-AMD participants and the NEI-AMD Research Groups for their valuable contributions to this research. Extant GWA study findings were published by Fritsche et al. [23] JPSG was supported by the NEI Intramural Research Program. NR 107 TC 0 Z9 0 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2014 VL 14 IS 7 BP 814 EP 832 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO0QN UT WOS:000341016100003 PM 25109799 ER PT S AU Keck, TM Burzynski, C Shi, L Newman, AH AF Keck, Thomas M. Burzynski, Caitlin Shi, Lei Newman, Amy Hauck BE Dwoskin, LP TI Beyond Small-Molecule SAR: Using the Dopamine D3 Receptor Crystal Structure to Guide Drug Design SO EMERGING TARGETS & THERAPEUTICS IN THE TREATMENT OF PSYCHOSTIMULANT ABUSE SE Advances in Pharmacology LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; PROTEIN-COUPLED RECEPTORS; POTENTIAL ANTIPSYCHOTIC AGENT; CONDITIONED PLACE PREFERENCE; FUNCTIONALIZED LINKING CHAINS; PROGRESSIVE RATIO SCHEDULES; CHRONIC BUSPIRONE TREATMENT; ABUSE THERAPEUTIC AGENTS; HUMAN COCAINE FATALITIES; HIGH-AFFINITY STATE AB The dopamine D3 receptor is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia, restless leg syndrome, and drug addiction. The high protein sequence homology between the D3 and D2 receptors has posed a challenge to developing D3 receptor-selective ligands whose behavioral actions can be attributed to D3 receptor engagement, in vivo. However, through primarily small-molecule structure-activity relationship (SAR) studies, a variety of chemical scaffolds have been discovered over the past two decades that have resulted in several D3 receptor-selective ligands with high affinity and in vivo activity. Nevertheless, viable clinical candidates remain limited. The recent determination of the high-resolution crystal structure of the D3 receptor has invigorated structure-based drug design, providing refinements to the molecular dynamic models and testable predictions about receptor-ligand interactions. This chapter will highlight recent preclinical and clinical studies demonstrating potential utility of D3 receptor-selective ligands in the treatment of addiction. In addition, new structure-based rational drug design strategies for D3 receptor-selective ligands that complement traditional small-molecule SAR to improve the selectivity and directed efficacy profiles are examined. C1 [Keck, Thomas M.; Burzynski, Caitlin; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Shi, Lei] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. [Shi, Lei] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Keck, Thomas/G-9798-2012 OI Keck, Thomas/0000-0003-1845-9373 FU Intramural NIH HHS [Z01 DA000424-09]; NIDA NIH HHS [DA023694, K99 DA023694, R00 DA023694] NR 129 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-12-420177-4; 978-0-12-420118-7 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2014 VL 69 BP 267 EP 300 DI 10.1016/B978-0-12-420118-7.00007-X PG 34 WC Substance Abuse; Pharmacology & Pharmacy SC Substance Abuse; Pharmacology & Pharmacy GA BB1OT UT WOS:000341244700008 PM 24484980 ER PT J AU Aurioles-Garibay, A Hernandez-Andrade, E Romero, R Qureshi, F Ahn, H Jacques, SM Garcia, M Yeo, L Hassan, SS AF Aurioles-Garibay, Alma Hernandez-Andrade, Edgar Romero, Roberto Qureshi, Faisal Ahn, Hyunyoung Jacques, Suzanne M. Garcia, Maynor Yeo, Lami Hassan, Sonia S. TI Prenatal Diagnosis of a Placental Infarction Hematoma Associated with Fetal Growth Restriction, Preeclampsia and Fetal Death: Clinicopathological Correlation SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE Stillbirth; Placental lesions; Ultrasound; Doppler velocimetry ID LATE-ONSET PREECLAMPSIA; CORONARY BLOOD-FLOW; DUCTUS VENOSUS; UMBILICAL ARTERY; AORTIC ISTHMUS; PATHOLOGICAL CORRELATION; MATERNAL UNDERPERFUSION; ADVERSE PREGNANCY; 2ND TRIMESTER; FETUSES AB The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma. (C) 2014 S. Karger AG, Basel C1 [Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M.; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M.; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Harper Univ Hosp, Dept Pathol, Detroit, MI 48201 USA. [Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM ehernand@med.wayne.edu; romeror@mail.nih.gov FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH), and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 65 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 EI 1421-9964 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PY 2014 VL 36 IS 2 BP 154 EP 161 DI 10.1159/000357841 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AN7XU UT WOS:000340815100009 PM 24852332 ER PT J AU Whitworth, C Oliver, B AF Whitworth, Cale Oliver, Brian TI Flipping the doublesex switch with a piRNA SO GENOME BIOLOGY LA English DT Editorial Material ID BOMBYX-MORI; SEX DETERMINATION; W-CHROMOSOME; SILKWORM; GENE; LETHAL AB Recent work in the silkworm Bombyx mori has uncovered a novel Piwi-interacting RNA regulator of the sex determination switch doublesex. C1 [Whitworth, Cale; Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Whitworth, C (reprint author), NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM cale.whitworth@nih.gov FU Intramural NIH HHS NR 8 TC 1 Z9 1 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 6 AR 118 DI 10.1186/gb4181 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AO3WZ UT WOS:000341269300016 PM 25002081 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Incorporating Gene-Environment Interaction in Testing for Association with Rare Genetic Variants SO HUMAN HEREDITY LA English DT Article DE Rare variant analysis; Gene-environment interaction; Sequence kernel association test; Joint test; Generalized linear mixed model ID GENERALIZED LINEAR-MODELS; GENOME-WIDE; NORMAL VARIABLES; QUADRATIC-FORMS; COMMON DISEASES; MIXED MODELS; REGRESSION; METAANALYSIS AB Objectives: The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants. Methods: In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions. Results: We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study. Conclusion: Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient. (C) 2014 S. Karger AG, Basel C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Chen, Han] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Dupuis, J (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM dupuis@bu.edu OI Chen, Han/0000-0002-9510-4923 FU NIH [R01 DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and Blood Institute (NHLBI); Boston University [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278] FX The authors would like to thank Dr. Xinyi Lin for sharing the R package iSKAT to perform GESAT-W. This research was partially supported by NIH awards R01 DK078616, U01 DK85526, and K24 DK080140. A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medicine Campus. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (contract No. N01-HC-25195). This work was partially supported by a contract with Affymetrix, Inc. for genotyping services (contract No. N02-HL-6-4278). NR 29 TC 1 Z9 1 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2014 VL 78 IS 2 BP 81 EP 90 DI 10.1159/000363347 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AN7WW UT WOS:000340812700003 PM 25060534 ER PT J AU Mcgowen, MR Erez, O Romero, R Wildman, DE AF Mcgowen, Michael R. Erez, Offer Romero, Roberto Wildman, Derek E. TI The evolution of embryo implantation SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE mammal; phylogeny; gene; implantation; superficial; interstitial ID LEUKEMIA INHIBITORY FACTOR; EARLY-PREGNANCY; RHESUS-MONKEY; MATRIX METALLOPROTEINASES; DELAYED IMPLANTATION; TISSUE INHIBITORS; RAT UTERUS; EXTRACELLULAR-MATRIX; MUSTELIDAE MAMMALIA; MESSENGER-RNA AB Embryo implantation varies widely in placental mammals. We review this variation in mammals with a special focus on two features: the depth of implantation and embryonic diapause. We discuss the two major types of implantation depth, superficial and interstitial, and map this character on a well-resolved molecular phylogenetic tree of placental mammals. We infer that relatively deep interstitial implantation has independently evolved at least eight times within placental mammals. Moreover, the superficial type of implantation represents the ancestral state for placental mammals. In addition, we review the genes involved in various phases of implantation, and suggest a future direction in investigating the molecular evolution of implantation-related genes. C1 [Mcgowen, Michael R.; Wildman, Derek E.] Wayne State Univ, Ctr Mol Med & Genet, Sch Med, Detroit, MI 48201 USA. [Erez, Offer] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. [Romero, Roberto; Wildman, Derek E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Romero, Roberto; Wildman, Derek E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Romero, Roberto; Wildman, Derek E.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. RP Wildman, DE (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Sch Med, 3240 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. EM dwildman@wayne.edu FU National Science Foundation [BCS-0827546] FX The authors would like to acknowledge the contribution of Caoyi Chen in digitizing the previously published data of H. W. Mossman. The National Science Foundation (BCS-0827546) supported a portion of the first author's (MM) salary. NR 66 TC 6 Z9 7 U1 5 U2 22 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 EI 1696-3547 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2014 VL 58 IS 2-4 BP 155 EP 161 DI 10.1387/ijdb.140020dw PG 7 WC Developmental Biology SC Developmental Biology GA AN6JZ UT WOS:000340702100011 PM 25023681 ER PT J AU Fritz, R Jain, C Armant, DR AF Fritz, Rani Jain, Chandni Armant, D. Randall TI Cell signaling in trophoblast-uterine communication SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE growth factors; trophoblast; endometrium; blastocyst; signaling ID LEUKEMIA INHIBITORY FACTOR; EPIDERMAL-GROWTH-FACTOR; ENDOMETRIAL EPITHELIAL-CELLS; HUMAN EMBRYO IMPLANTATION; FACTOR GENE-EXPRESSION; FACTOR-RECEPTOR GENE; OUTGROWTH IN-VITRO; SERUM-FREE MEDIUM; MOUSE UTERUS; INDIAN HEDGEHOG AB Intricate and precise communication between the blastocyst and the uterus orchestrates embryo implantation. However, many questions remain unanswered regarding the molecular complexities of implantation. On-time implantation requires a receptive uterus and a mature blastocyst with trophoblast cells capable of adhering to and invading the endometrium. Defects in uterine receptivity or embryo/uterine signaling can cause implantation failure or early pregnancy loss, whereas deficient trophoblast differentiation can generate placental abnormalities that produce adverse pregnancy outcomes. This review will discuss several examples of signaling pathways that regulate trophoblast and uterine development during this period. Leukemia inhibitory factor is involved in uterine priming for implantation. The epidermal growth factor signaling system contributes to trophoblast-uterine communication, as well as trophoblast adhesion and invasion. Indian hedgehog signaling synchronizes tissue compartments within the uterus, and WNT signaling mediates numerous interactions within the implantation site and developing placenta. The autocrine, paracrine and juxtacrine interactions mediated by these signaling pathways contribute significantly to the establishment of pregnancy, although there are many other known and yet to be discovered factors that synchronize the maternal and embryonic developmental programs. C1 [Fritz, Rani; Jain, Chandni; Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Fritz, Rani; Jain, Chandni] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Physiol, Detroit, MI 48201 USA. [Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Anat & Cell Biol, Detroit, MI 48201 USA. [Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA. RP Armant, DR (reprint author), Wayne State Univ, Mott Ctr Human Growth & Dev, 275 East Hancock St, Detroit, MI 48201 USA. EM D.Armant@Wayne.edu OI Armant, D. Randall/0000-0001-5904-9325 FU Intramural Research Program of the National Institute for Child Health and Human Development, National Institutes of Health; NIH [HD071408]; W.K. Kellogg Foundation FX Supported in part by the Intramural Research Program of the National Institute for Child Health and Human Development, National Institutes of Health and grants from the NIH (HD071408) and the W.K. Kellogg Foundation. NR 133 TC 16 Z9 16 U1 4 U2 12 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 EI 1696-3547 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2014 VL 58 IS 2-4 BP 261 EP 271 DI 10.1387/ijdb.140011da PG 11 WC Developmental Biology SC Developmental Biology GA AN6JZ UT WOS:000340702100022 PM 25023692 ER PT J AU Snyder, RJ Hussain, S Rice, AB Garantziotis, S AF Snyder, Ryan J. Hussain, Salik Rice, Annette B. Garantziotis, Stavros TI Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE multiwalled carbon nanotubes; bronchial epithelium; transepithelial electrical resistance; cytoskeleton; morphology; human ID INFLAMMATORY RESPONSES; STEM-CELLS; IN-VITRO; CYTOTOXICITY; MICE; INSTILLATION; LENGTH; LUNG AB Multiwalled carbon nanotubes (MWCNTs) have seen increasing application in consumer products over the past decade, resulting in an increasing risk of human exposure. While numerous toxicological studies have been performed using acute high doses of various carbonaceous nanomaterials, the effects of longer-term, low doses of MWCNTs remain relatively unexplored. This study examined bronchoscopy-derived healthy human bronchial epithelial cells exposed in submerged culture to noncytotoxic doses of MWCNTs over 7 days. Under these conditions, doses as low as 3 g/mL caused altered cell morphology, superficially resembling fibroblasts. Electrical impedance of the epithelial monolayer was greatly reduced following MWCNT exposure. However, Western blot and polymerase chain reaction showed no elevated expression of the fibroblast markers, vimentin, a-smooth muscle actin, or fibronectin, indicating that a mechanism other than epithelial-mesenchymal transition may be responsible for the changes. Phalloidin and tubulin immunostaining showed disruption of the cytoskeleton, and confocal imaging showed a reduction of the tight junction proteins, zona occludens 1 and occludin. We propose that MWCNTs interfere with the cytoskeleton of the lung epithelium, which can result in a harmful reduction in barrier function over time, even at noncytotoxic doses. C1 [Snyder, Ryan J.; Hussain, Salik; Rice, Annette B.; Garantziotis, Stavros] NIEHS, Clin Res Unit, NIH, Res Triangle Pk, NC 27709 USA. RP Snyder, RJ (reprint author), NIEHS, Clin Res Unit, 111 TW Alexander Dr, Durham, NC 27709 USA. EM snyder3@niehs.nih.gov RI Hussain, Salik/O-1687-2016; Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural Research Program of the National Institutes of Health (NEH), National Institute of Environmental Health Science (NIEHS) FX This research was supported (in part) by the Intramural Research Program of the National Institutes of Health (NEH), National Institute of Environmental Health Science (NIEHS). We would like to thank Dr James C Bonner (North Carolina State University) for providing us with the MWCNTs used in this study. We would also like to thank Dr John Roberts and Robert Wine (NIH, NIEHS) for their assistance with the ECIS device, and Dr Jeff Tucker and Dr Agnes Janoshazi (NIH, NIEHS), for their assistance with obtaining the confocal images. We also thank Connie Cummings and Deloris Sutton (NIH, NIEHS) for their work with TEM. NR 30 TC 6 Z9 6 U1 0 U2 5 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2014 VL 9 BP 4093 EP 4105 DI 10.2147/IJN.S65567 PG 13 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AN8QP UT WOS:000340869100004 PM 25187712 ER PT J AU Dickherber, A Sorg, B Divi, R Ganguly, A Ossandon, M AF Dickherber, Anthony Sorg, Brian Divi, Rao Ganguly, Aniruddha Ossandon, Miguel TI Guest editorial: funding for innovative cancer-relevant technology development SO LAB ON A CHIP LA English DT Editorial Material ID TUMOR-CELLS; SPECTROSCOPY; DELIVERY; PLATFORM C1 [Dickherber, Anthony; Sorg, Brian; Divi, Rao; Ganguly, Aniruddha; Ossandon, Miguel] NCI, NIH, Bethesda, MD 20892 USA. RP Dickherber, A (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM dickherberaj@mail.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 18 BP 3445 EP 3446 DI 10.1039/c4lc90059f PG 2 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AN3GQ UT WOS:000340474300001 PM 25032520 ER PT J AU Chen, T Chen, SH Zhou, JH Liang, DH Chen, XY Huang, YY AF Chen, Tao Chen, Shouhui Zhou, Jihan Liang, Dehai Chen, Xiaoyuan Huang, Yanyi TI Transient absorption microscopy of gold nanorods as spectrally orthogonal labels in live cells SO NANOSCALE LA English DT Article ID PHOTOTHERMAL THERAPY; NANOPARTICLES; SPECTROSCOPY; SCATTERING; DYNAMICS; CANCER; ENHANCEMENT; ELECTRON; DELIVERY; SILVER AB Gold nanorods (AuNRs) have shown great potential as bio-compatible imaging probes in various biological applications. Probing nanomaterials in live cells is essential to reveal the interaction between them. In this study, we used a transient absorption microscope to selectively image AuNRs in live cells. The transient absorption signals were monitored through lock- in amplification. This provides a new way of observing AuNRs with no interference from background autofluorescence. C1 [Chen, Tao; Huang, Yanyi] Peking Univ, Coll Engn, Biodynam Opt Imaging Ctr BIOPIC, Beijing 100871, Peoples R China. [Chen, Shouhui] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai 200030, Peoples R China. [Zhou, Jihan; Liang, Dehai] Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. [Zhou, Jihan; Liang, Dehai] Peking Univ, Key Lab Polymer Chem & Phys, Minist Educ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; yanyi@pku.edu.cn RI Huang, Yanyi/D-1832-2009 OI Huang, Yanyi/0000-0002-7297-1266 FU Ministry of Science and Technology of China [2011CB809106]; National Natural Science Foundation of China [21222501, 91313302]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX The authors thank Dr Brian Saar and Prof. X. Sunney Xie for providing the lock-in amplifier. This work was financially supported by the Ministry of Science and Technology of China (Grant no. 2011CB809106), the National Natural Science Foundation of China (Grant no. 21222501 and 91313302), and the intramural research program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 24 TC 8 Z9 8 U1 4 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2014 VL 6 IS 18 BP 10536 EP 10539 DI 10.1039/c4nr03413a PG 4 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AO0RY UT WOS:000341020700013 PM 25098209 ER PT B AU Perkins, MR Brenchley, JM AF Perkins, Molly R. Brenchley, Jason M. BE Ansari, AA Silvestri, G TI Gastrointestinal Immunity in Natural Hosts of Simian Immunodeficiency Virus SO NATURAL HOSTS OF SIV: IMPLICATION IN AIDS LA English DT Article; Book Chapter ID T-CELL DEPLETION; INFECTED SOOTY MANGABEYS; AFRICAN-GREEN MONKEYS; ACTIVE ANTIRETROVIRAL THERAPY; NONPATHOGENIC SIV INFECTION; RHESUS MACAQUES; HIV-1 INFECTION; MICROBIAL TRANSLOCATION; LENTIVIRAL INFECTIONS; VIRAL REPLICATION C1 [Perkins, Molly R.; Brenchley, Jason M.] NIAID, Program Tissue Immun & Repair, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Perkins, MR (reprint author), NIAID, Program Tissue Immun & Repair, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-405167-6; 978-0-12-404734-1 PY 2014 BP 123 EP 134 DI 10.1016/B978-0-12-404734-1.00007-3 PG 12 WC Immunology; Virology SC Immunology; Virology GA BB1EK UT WOS:000341036900007 ER PT S AU Douville, RN Nath, A AF Douville, Renee N. Nath, Avindra BE Tselis, AC Booss, J TI Human endogenous retroviruses and the nervous system SO NEUROVIROLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; SCLEROSIS-ASSOCIATED RETROVIRUS; LONG TERMINAL REPEAT; REVERSE-TRANSCRIPTASE ACTIVITY; AMYOTROPHIC-LATERAL-SCLEROSIS; CHRONIC-FATIGUE-SYNDROME; BLOOD MONONUCLEAR-CELLS; ZINC-FINGER PROTEIN; HERV-W ENV; I HTLV-I C1 [Douville, Renee N.] Univ Winnipeg, Dept Microbiol, Winnipeg, MB R3B 2E9, Canada. [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. RP Nath, A (reprint author), Room 7C-103,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM natha@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003130-01] NR 217 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-53488-0; 978-0-702-04539-4 J9 HAND CLINIC PY 2014 VL 123 BP 465 EP 485 PG 21 WC Clinical Neurology SC Neurosciences & Neurology GA BB1EM UT WOS:000341048300024 PM 25015500 ER PT J AU Ghosh, AK Schiltz, GE Rusere, LN Osswald, HL Walters, DE Amano, M Mitsuya, H AF Ghosh, Arun K. Schiltz, Gary E. Rusere, Linah N. Osswald, Heather L. Walters, D. Eric Amano, Masayuki Mitsuya, Hiroaki TI Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1-P2 ligands SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; DRUG-RESISTANT HIV; ANTIRETROVIRAL THERAPY; UNSATURATED ALDEHYDES; METATHESIS CATALYSTS; CRYSTAL-STRUCTURES; IN-VITRO; ACIDS; RESOLUTION; STRATEGY AB A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16-to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound 8a containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity. C1 [Ghosh, Arun K.; Schiltz, Gary E.; Rusere, Linah N.; Osswald, Heather L.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Schiltz, Gary E.; Rusere, Linah N.; Osswald, Heather L.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Walters, D. Eric] Rosalind Franklin Univ Med & Sci, Dept Pharmaceut Sci, N Chicago, IL 60064 USA. [Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NIH, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu RI Amano, Masayuki/N-7407-2016 OI Amano, Masayuki/0000-0003-0516-9502 FU National Institute of Health [GM 53386]; Center for Cancer Research, National Cancer Institute, National Institutes of Health; Ministry of Education, Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho); Ministry of Health, Welfare, and Labor of Japan [Kosei Rohdosho: H15-AIDS-001]; Kumamoto University [78] FX Financial support for this work was provided by the National Institute of Health (GM 53386). This work was also supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health and in part by a Grant-in-aid for Scientific Research (Priority Areas) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho), a Grant for Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan (Kosei Rohdosho: H15-AIDS-001), and the Grant to the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Re-emerging Infectious Diseases (Renkei Jigyo: No. 78, Kumamoto University) of Monbu-Kagakusho. We would like to thank Dr Kalapala Venkateswara Rao (Purdue University) for helpful discussions. NR 36 TC 6 Z9 7 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2014 VL 12 IS 35 BP 6842 EP 6854 DI 10.1039/c4ob00738g PG 13 WC Chemistry, Organic SC Chemistry GA AO0TF UT WOS:000341024300013 PM 25050776 ER PT J AU Chung, HS Gopich, IV AF Chung, Hoi Sung Gopich, Irina V. TI Fast single-molecule FRET spectroscopy: theory and experiment SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID RESONANCE ENERGY-TRANSFER; HIDDEN MARKOV-MODELS; MULTIPARAMETER FLUORESCENCE DETECTION; ALTERNATING-LASER EXCITATION; TRANSITION PATH TIMES; CONFORMATIONAL DYNAMICS; PHOTON STATISTICS; PROTEIN COLLAPSE; TRAJECTORIES; KINETICS AB Single-molecule spectroscopy is widely used to study macromolecular dynamics. Although this technique provides unique information that cannot be obtained at the ensemble level, the possibility of studying fast molecular dynamics is limited by the number of photons detected per unit time ( photon count rate), which is proportional to the illumination intensity. However, simply increasing the illumination intensity often does not help because of various photophysical and photochemical problems. In this Perspective, we show how to improve the dynamic range of single-molecule fluorescence spectroscopy at a given photon count rate by considering each and every photon and using a maximum likelihood method. For a photon trajectory with recorded photon colors and inter-photon times, the parameters of a model describing molecular dynamics are obtained by maximizing the appropriate likelihood function. We discuss various likelihood functions, their applicability, and the accuracy of the extracted parameters. The maximum likelihood method has been applied to analyze the experiments on fast two-state protein folding and to measure transition path times. Utilizing other information such as fluorescence lifetimes is discussed in the framework of two-dimensional FRET efficiency-lifetime histograms. C1 [Chung, Hoi Sung; Gopich, Irina V.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Chung, HS (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM chunghoi@niddk.nih.gov; irinag@niddk.nih.gov RI Chung, Hoi Sung/C-2624-2009 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX We thank W. A. Eaton, A. Szabo, and A. M. Berezhkovskii for numerous helpful discussions and comments. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 90 TC 15 Z9 15 U1 7 U2 40 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2014 VL 16 IS 35 BP 18644 EP 18657 DI 10.1039/c4cp02489c PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AO4GV UT WOS:000341295500002 PM 25088495 ER PT B AU Carey, W Lim, W Reineck, A Williams, R AF Carey, Will Lim, Wendell Reineck, Adam Williams, Reid BA Ginsberg, AD Calvert, J Schyfter, P Elfick, A Endy, D BF Ginsberg, AD Calvert, J Schyfter, P Elfick, A Endy, D TI Living among Living Things SO SYNTHETIC AESTHETICS: INVESTIGATING SYNTHETIC BIOLOGY'S DESIGNS ON NATURE LA English DT Article; Book Chapter C1 [Carey, Will; Reineck, Adam] IDEO, Palo Alto, CA 94301 USA. [Lim, Wendell] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. [Lim, Wendell] Howard Hughes Med Inst, Chevy Chase, MD USA. [Lim, Wendell] Univ Calif San Francisco, NIH, Ctr Syst & Synthet Biol, San Francisco, CA 94143 USA. [Lim, Wendell] NIH, Cell Prop Lab, Roadmap Nanomed Dev Ctr, Bethesda, MD USA. [Lim, Wendell] Natl Sci Fdn, Synthet Biol Engn Res Ctr, Arlington, VA 22230 USA. [Reineck, Adam] CGAP, Washington, DC USA. [Williams, Reid] Univ Calif San Francisco, Lab Wendell Lim, San Francisco, CA 94143 USA. RP Carey, W (reprint author), IDEO, Palo Alto, CA 94301 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-32159-4; 978-0-262-01999-6 PY 2014 BP 169 EP 180 PG 12 WC Biotechnology & Applied Microbiology; History & Philosophy Of Science; Social Sciences, Biomedical SC Biotechnology & Applied Microbiology; History & Philosophy of Science; Biomedical Social Sciences GA BA7JM UT WOS:000337605500010 ER PT J AU Klinger, R Colloca, L AF Klinger, Regine Colloca, Luana TI Approaches to a Complex Phenomenon The Basic Mechanisms and Clinical Applications of Placebo Effects SO ZEITSCHRIFT FUR PSYCHOLOGIE-JOURNAL OF PSYCHOLOGY LA English DT Editorial Material ID ANALGESIA C1 [Klinger, Regine] Univ Hamburg, Dept Psychol, Psychotherapeut Outpatient Clin, D-20146 Hamburg, Germany. [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Klinger, R (reprint author), Univ Hamburg, Dept Psychol, Outpatient Clin Behav Therapy, Von Melle Pk 5, D-20146 Hamburg, Germany. EM rklinger@uni-hamburg.de FU Intramural NIH HHS [Z99 AT999999] NR 15 TC 0 Z9 0 U1 1 U2 9 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 2190-8370 EI 2151-2604 J9 Z PSYCHOL JI Z. Psychol.-J. Psychol. PY 2014 VL 222 IS 3 BP 121 EP 123 DI 10.1027/2151-2604/a000175 PG 3 WC Psychology, Multidisciplinary SC Psychology GA AO4CU UT WOS:000341284600001 PM 25485186 ER PT J AU Colloca, L Jonas, WB Killen, J Miller, FG Shurtleff, D AF Colloca, Luana Jonas, Wayne B. Killen, John, Jr. Miller, Franklin G. Shurtleff, David TI Reevaluating the Placebo Effect in Medical Practice SO ZEITSCHRIFT FUR PSYCHOLOGIE-JOURNAL OF PSYCHOLOGY LA English DT Review DE placebo; expectations; ethics; policy; patient-clinician communication ID CLINICAL-PRACTICE; INTERVENTIONS; MECHANISMS; OUTCOMES; TRIAL AB Recent findings from placebo research corroborate the evidence that the placebo effect represents a promising model to shed new light on brain-mind-body interactions. In particular, this research has partially elucidated the role of how patients' expectations and the quality of physician-patient communication can influence the efficacy of interventions and overall clinical outcomes. Accordingly, the study of the placebo effect should be incorporated in the core clinical practice curriculum of all health practitioners. While the growing knowledge about the placebo effect points to it being an irreducible primary reality of medical practice, an ethical analysis aimed at avoiding the misuse of placebos and maximizing beneficial placebo effects is needed. C1 [Colloca, Luana; Killen, John, Jr.; Shurtleff, David] NCCAM, Bethesda, MD USA. [Colloca, Luana] NIMH, Bethesda, MD 20892 USA. [Colloca, Luana; Miller, Franklin G.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Jonas, Wayne B.] Samueli Inst, Alexandria, VA USA. RP Colloca, L (reprint author), NIH, Ctr Clin, 10 Ctr Dr,10-1C154, Bethesda, MD 20892 USA. EM luana.colloca@nih.gov OI Colloca, Luana/0000-0002-6503-4709 FU Intramural NIH HHS [Z99 AT999999] NR 28 TC 7 Z9 7 U1 0 U2 3 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 2190-8370 EI 2151-2604 J9 Z PSYCHOL JI Z. Psychol.-J. Psychol. PY 2014 VL 222 IS 3 BP 124 EP 127 DI 10.1027/2151-2604/a000177 PG 4 WC Psychology, Multidisciplinary SC Psychology GA AO4CU UT WOS:000341284600002 PM 25360397 ER PT J AU Kranick, SM Nath, A AF Kranick, Sarah M. Nath, Avindra BE Poewe, W Jankovic, J TI Movement disorders in HIV- and AIDS-related central nervous system infections SO MOVEMENT DISORDERS IN NEUROLOGIC AND SYSTEMIC DISEASE LA English DT Article; Book Chapter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-DEFICIENCY-SYNDROME; CEREBRAL TOXOPLASMOSIS; NEUROCOGNITIVE DISORDERS; CLINICAL-FEATURES; DEMENTIA COMPLEX; HOLMES TREMOR; PARKINSONISM; DISEASE C1 [Kranick, Sarah M.; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. RP Kranick, SM (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02461-8 PY 2014 BP 89 EP 98 D2 10.1017/CBO9781139175845 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA BA7VU UT WOS:000337803000008 ER EF